The five-story Marriott had been a favorite spot for foreigners as well as Pakistani politicians and business people to stay and socialize in Islamabad despite repeated militant attacks on it. The bomb went off close to 8 p.m., when four restaurants inside would have been packed with diners at the hour that Muslims break their daily fast during the holy month of Ramadan.
"I didn't understand what it was, but it was like the world is finished," said Mohammad Sultan, a hotel employee who was in the lobby when the bomb exploded.
The blast left a vast crater some 30 feet deep in front of the building. Rescuers ferried a stream of bloodied bodies from the gutted structure after the attack, then pulled back for fear that it could collapse. Early on Sunday, investigators combed the gaping hole for evidence and rescue teams searched the building room by room.
The fire was still burning more than six hours after the blast and had gutted the hotel, sending up a thick pall of smoke over the area.
The death toll was likely to rise once the flames are extinguished and rescuers can thoroughly search the devastation.
The bombing came just hours after President Asif Ali Zardari made his first address to Parliament, less than a mile away from the hotel, and days ahead of the new leader's meeting with President Bush Tuesday in New York on the sidelines of the U.N. General Assembly.
Rehman Malik, the head of the Interior Ministry, told The Associated Press it was unclear who was behind the attack and there had been no claim of responsibility. But authorities had received intelligence that there might be militant activity linked to Zardari's address to Parliament and security had been tightened, he said.
Analysts said the attack is a warning from Islamic extremists to the new civilian leadership of Pakistan that it should end already-strained cooperation with the United States to pursue al-Qaida and Taliban militants entrenched in the lawless tribal region along the border with Afghanistan.
Terrorism researcher Evan Kohlmann said the attack was almost certainly either Al-Qaida or Pakistani Taliban.
"We are looking at either Al Qaida or Tehrik-e-Taliban (Pakistan)," he said. "It seems that someone has a firm belief that hotels like the Marriott are serving as 'barracks' for western diplomats and intel personnel, and they are gunning pretty hard for them."
Zardari reappeared after midnight on state television to condemn the "cowardly attack." He said he understood the victims' pain because he had buried his own wife - assassinated former Prime Minister Benazir Bhutto - in December.
"Make this pain your strength," he said. "This is a menace, a cancer in Pakistan which we will eliminate. We will not be scared of these cowards," he said.
Witnesses and officials said the dump truck exploded about 60 feet away from the hotel at two heavy metal barriers blocking the entrance. The location of the hotel made it vulnerable. It lies just off a busy thoroughfare, less than a mile from the presidential offices and Parliament. The security gate was well within the range of the blast wave.
The explosion reverberated throughout Islamabad and shattered windows hundreds of yards away.
"The fire has eaten the entire building," said Mohammed Ali, an emergency service official at the scene. He said that after an initial chaotic search to find survivors, rescue teams had only been able to make two brief forays inside but found no bodies or survivors and had to retreat quickly.
Teams of firefighters sprayed water from firehoses as bulldozers cleared debris.
Earlier, a U.S. State Department official led three colleagues through the rubble from the charred building, one of them bleeding heavily from a wound on the side of his head. One of the four, who identified himself only as Tony, said they had been moving toward the rear of a Chinese restaurant inside the hotel after a first, small blast when a second explosion hurled them against the back wall.
"Then we saw a big truck coming to the gates," he said. "After that, it was just smoke and darkness."
Mohammed Asghar, a worker from a nearby office with a makeshift bandage round his head, said there was more than one man in the truck and that they had argued with the hotel guards.
"Then there was a flash of light, the truck caught fire and then exploded with an enormous bang," he said.
Senior police official Asghar Raza Gardaizi estimated the truck carried more than 2,200 pounds of explosives. He said in the midst of the rescue operation that at least 40 people were killed and many more feared buried in the rubble.
However, Kamal Shah, a senior Interior Ministry official, said earlier Sunday he knew of only 38 confirmed deaths.
Associated Press reporters saw at least nine bodies scattered at the scene. Scores of people, including foreigners, were running out - some of them stained with blood.
Information Minister Sherry Rehman said at least 250 people were wounded. Hospital staff and other officials said 21 foreigners were among the injured, including four Britons, four Germans, two Americans and one each from Denmark, Saudi Arabia, Morocco, Libya, Lebanon and Afghanistan. The Saudi ambassador said several staff from the kingdom's national airline were missing.
At one hospital, relatives were trying to identify dead bodies covered in bloodstained white sheets in the morgue. Some of the distraught family members wailed and hugged each other while police filled out forms for those claiming the dead. Some of the injured foreigners with their wounds bandaged were taken out in wheelchairs.
Pakistan faces a raging insurgency by the Taliban in the tribal regions along the border with Afghanistan, where Western governments worry that al-Qaida militants could be plotting more attacks on their cities. Security officials say the two groups work together to carry out attacks in Afghanistan and Pakistan.
Officials have warned that increasing U.S. cross-border raids on Pakistani territory recently could fuel violent extremism.
President Bush said the attack was "a reminder of the ongoing threat faced by Pakistan, the United States, and all those who stand against violent extremism."
State Department spokesman Sean McCormack said at least one American was killed and several were wounded.
"This barbaric attack comes during the month of Ramadan, only underscoring that those responsible have no respect for the principles of their faith. This strike to the heart of the Pakistani capital leaves no doubt as to the intentions of these extremist elements. Their goal is to create mayhem and weaken the institutions of government so that they may operate unfettered while spreading their intolerance."
U.N. Secretary-General Ban Ki-moon strongly condemned the "heinous terrorist attack," and said "no cause can justify the indiscriminate targeting of civilians."
IntelCenter, a group which monitors al-Qaida communications, said senior al-Qaida leader Mustafa Abu al-Yazid, who claimed the June Danish Embassy bombing in Islamabad, threatened additional attacks against Western interests in Pakistan in a video timed to the recent anniversary of the Sept. 11 attacks.
U.S. Embassy spokesman Lou Fintor said officials were trying to account for embassy staff and any other Americans affected. Ambulances rushed to the area, picking their way through the charred carcasses of vehicles that had been in the street outside. Windows in buildings hundreds of yards away were shattered. Tropical fish from the tanks inside lay among the torn furnishings in the entrance area.
"We live in a dangerous world and this is a terrible tragedy. We grieve for those people who died, or were injured, and their families," Bill Marriott, chairman and CEO of Marriott International, said in a statement.
The hotel served as the headquarters for the international media during the 2001 war against the Taliban in neighboring Afghanistan. Its 290 rooms and suites and popular health club stood in a plot surrounded by government office buildings less than a mile from the president's office and Parliament. It had been targeted before.
In January 2007, a security guard blocked a suicide bomber who triggered a blast just outside the Marriott, killing the guard and wounding seven other people.
Pakistan has faced a wave of militant violence in recent months following army-led offensives against insurgents in its border regions, including several in the capital.
The country's deadliest suicide bombing was on Oct. 18, 2007 and targeted Bhutto, who survived. It killed some 150 people in Karachi during celebrations welcoming her home from exile. Bhutto was assassinated in a subsequent attack on Dec. 27.
On Aug. 21, 2008, suicide bombers blew themselves up at two gates into mammoth weapons factory in town of Wah, killing at least 67 people and wounding more than 70.
Associated Press writers Asif Shahzad, Zarar Khan, Munir Ahmad in Islamabad and Edith M. Lederer at the United Nations contributed to this report.