A blast killed at least 22 people in the southwestern city of Quetta at a Shiite procession calling for solidarity with Palestinians, Police Chief Ghulam Shabir Sheikh said. Police said dozens were wounded and some were in critical condition.
Some Shiite youths fired in the air after the blast, and Qazi Abdul Wahid, a senior police official, said officers were trying to control the situation.
Shiite leader Allama Abbas Kumaili appealed to participants to remain peaceful.
"We understand these are attempts to bring Sunni and Shiite sects against each other," he said.
The attack in Quetta was the second this week on Pakistani Shiites, who by some estimates comprise about 20 percent of the population in the mostly Sunni Muslim country, although figures are imprecise and disputed.
A triple suicide attack Wednesday night killed 35 people at a Shiite ceremony in the eastern city of Lahore.
Kumaili said the attacks against minority sects were a result of government failure.
"Our government concentrates all its efforts to secure VIPs. Common men are not their priority," he said.
Government officials have said they cannot protect outdoor gatherings from attacks, and Interior Minister Rehman Malik called Thursday for Shiites to hold religious ceremonies indoors.
Baluchistan provincial police chief Malik Iqbal said officials had warned organizers of the Quetta ceremony to stick inside a security cordon after intelligence agents received reports about a possible terror attack.
"They violated the route," Iqbal said. "We had warned them not to extend their rally out of the cordon."
Wednesday's attack in Lahore, and a host of other assaults on religious minorities, was claimed by the hardline Sunni Pakistani Taliban, which is seeking to overthrow a Western-backed government shaken most recently by flooding that has caused massive displacement, suffering and economic damage.
Earlier Friday, a suicide attack on a mosque belonging to the minority Ahmadi sect killed at least one person and wounded several others in the northwest Pakistani town of Mardan.
Military and law-enforcement officials also have been battered by militant violence, particularly along the border with Afghanistan. Officials said a roadside bomb attack in the capital of the northwest's Khyber Pakhtunkhwa province Friday killed one police officer and wounded three others.
The floods, spawned by heavy rains weeks ago in Khyber Pakhtunkhwa and elsewhere in the mountains of northern Pakistan, have killed more than 1,600 people and affected about 20 million people. The waters are still swamping rich agricultural land in the southern provinces of Sindh and Punjab.
Flood victims say they have received little government help, and most assistance has come to them from private charities. The International Committee of the Red Cross warned Thursday that survivors' anger was beginning to hamper those aid efforts.
About 500 survivors blocked a key road in the Sindh town of Gharo on Friday to protest inadequate food and drinking water.
"We have blocked traffic today to draw government attention toward our problems. We are living at a government building without food," said Deedar Ahmad, 25, who said he fled with about 1,000 people from a nearby flooded village.
Survivor Ali Nawaz said the government had housed flood victims but was not providing food, electricity, water or adequate shelter.
"We cannot sleep because of the fears of snakes," he said.
The flooding, and anger over the government response, has raised fears about the stability of Pakistan's government, seen as a problematic but essential Western ally in the fight against Islamist militants in Afghanistan and Pakistan's own restive tribal areas.
The Pakistani Taliban has issued veiled threats against Western aid workers but a recent wave of attacks have focused instead on religious minorities, particularly Shiites and Ahmadis.
Police official Ahsanullah Khan said the bomber in Friday's attack on the Ahmadi mosque in the northwest town of Mardan appeared to have detonated himself after he was prevented from entering the building.
In May, two teams of seven militants armed with hand grenades, suicide vests and assault rifles attacked two Ahmadi mosques in Lahore, killing 97 and wounding dozens.
Many mainstream Muslims consider the Ahmadis heretics for believing that their founder, Mirza Ghulam Ahmad, was a savior foretold by the Quran, Islam's holy book. They say Ahmadis are defying the basic tenet of Islam that says Muhammad is the final prophet.
Ahmadis argue that their leader was the savior rather than a prophet.
Under pressure from Islamists, Pakistan in the 1970s declared Ahmadis a non-Muslim minority. Pakistani Ahmadis - who number between 3 million and 4 million - are prohibited from calling themselves Muslims or engaging in practices such as reciting Islamic prayers.
Khan reported from Peshawar. Associated Press Writer Vincent Thian contributed to this report from Gharo.