Amateur video footage purportedly from the center of Tehran showed an enraged crowd carrying away one of the casualties, chanting, "I'll kill, I'll kill the one who killed my brother." In several locations in the center of the capital, demonstrators fought back furiously against security forces, hurling stones and setting their motorcycles, cars and vans ablaze, according to video footage and pro-reform Web sites.
Demonstrations also took place in at least three other cities.
A close aide to Mousavi, a presidential contender in a disputed June election, said the 35-year-old nephew, Ali Mousavi, died of injuries in a Tehran hospital. The aide spoke on condition of anonymity because of fears of reprisals from the government.
Mousavi's Web site and another reformist Web site, Parlemannews.ir, also said Ali Mousavi died during clashes in which security forces reportedly fired on demonstrators.
The protesters in Tehran tried to cut off roads with burning barricades that filled the sky with billowing black smoke. One police officer was photographed with blood streaming down his face after he was set upon by the crowd in a blazing street.
The protests began with thousands of opposition supporters chanting "Death to the dictator," a reference to hard-line President Mahmoud Ahmadinejad, as they took to the streets in defiance of official warnings of a harsh crackdown on any demonstrations coinciding with a religious observance on Sunday. Iranians were marking Ashoura, commemorating the seventh-century death in battle of one of Shiite Islam's most beloved saints.
Security forces tried but failed to disperse protesters on a central Tehran street with tear gas, charges by baton-wielding officers and warning shots fired into the air. They then opened fire directly at protesters, killing at least three people, said witnesses and the pro-reform Web site Rah-e-Sabz. A fourth protester was shot dead on a nearby street, they said.
Witnesses said one victim was an elderly man who had a gunshot wound to the forehead. He was seen being carried away by opposition supporters with blood covering his face.
More than two dozen opposition supporters were injured, some of them seriously, with limbs broken from beatings, according to witnesses. There were also violent confrontations in at least three other major cities: Isfahan and Najafabad in central Iran and Shiraz in the south.
The clashes marked the bloodiest confrontation between protesters and security forces since the height of the unrest in the weeks after June's election. The opposition says Ahmadinejad won the election through massive vote fraud and that Mousavi was the true winner.
Reporters from foreign media organizations were barred from covering the demonstrations on Tehran's central Enghelab Street, or Revolution Street, and the reports of deaths could not be independently confirmed. Video footage circulating on the Web could also not be authenticated.
Ambulance sirens could be heard near the site of the protests.
The witnesses and opposition Web sites said angry protesters threw stones at security forces and set dozens of their motorbikes on fire. Police helicopters circled overhead as clouds of black smoke billowed into the sky over the capital.
Tehran's police chief denied officers fired on the crowd - or that they were even armed.
"No report of death has been sent to the police," Azizollah Rajabzadeh said, according to the semiofficial ISNA news agency. "No one has been killed. Police did not open fire and the present officers did not carry weapons."
Police had blocked streets leading to the center of the capital to try to prevent thousands of people from joining the protest. Still, many opposition supporters managed to break the security wall.
Fierce clashes also broke out Sunday between security forces and opposition supporters in the cities of Isfahan and Najafabad in central Iran, the Rah-e-Sabz Web site said.
Cell phone services were down and Internet connections were slowed to a crawl, as has happened during most other days of opposition protest in an apparent government attempt to limit publicity and prevent protesters from organizing.
Opposition activists have held a series of anti-government protests since the death of a dissident cleric last week.
The Dec. 20 death of the 87-year-old Grand Ayatollah Hossein Ali Montazeri, a sharp critic of Iran's leaders, has given a new push to opposition protests, which have endured despite a heavy security crackdown since the election.
His memorials have brought out not only the young, urban activists who filled the ranks of earlier protests, but also older, more religious Iranians who revered Montazeri on grounds of faith as much as politics. Tens of thousands marched in his funeral procession in the holy city of Qom on Monday, many chanting slogans against the government.
Iran's police chief, Gen. Ismail Ahmadi Moghaddam, had threatened tougher action against protesters on Sunday should they hold rallies.
Opposition leaders have used holidays and other symbolic days in recent months to stage anti-government rallies.
Iran is under pressure both from its domestic opposition within the country and from the United States and its European allies, which are pushing Iran to suspend key parts of its nuclear program.