The dead included a nephew of opposition leader Mir Hossein Mousavi, according to Mousavi's Web site, Kaleme.ir. The clashes were sure to deepen antagonism between the government and a reform movement that has shown resilience in the face of repeated crackdowns.
The street chaos coincided with commemorations of Shiite Islam's most important observance, Ashoura, fueling protesters' defiance with its message of sacrifice and dignity in the face of coercion.
Still, many demonstrators had not anticipated such harsh tactics by the authorities, despite police warnings of tougher action against any protests on the sacred day.
Amateur video footage purportedly from the center of Tehran showed an enraged crowd carrying away one casualty, chanting, "I'll kill, I'll kill the one who killed my brother." In several locations, demonstrators confronted security forces, hurling stones and setting their motorcycles, cars and vans ablaze, according to video footage and pro-reform Web sites.
Protesters tried to cut off roads with burning barricades. One police officer was photographed with blood streaming down his face after he was set upon by the crowd.
There were unconfirmed reports that four people died in protests in Tabriz in northwest Iran, the pro-reform Rah-e-Sabz Web site said. Fierce clashes also broke out in Isfahan and Najafabad in central Iran and Shiraz in the south, it said.
Mousavi's Web site said the nephew, Ali Mousavi, was shot in the back on Azadi Street, or Freedom Street, during clashes in which security forces reportedly fired on demonstrators, and was taken to Ibn Sina Hospital. It said Mousavi and other family members rushed to the hospital.
A close aide to Mousavi, a presidential contender in a disputed June election, said Ali Mousavi died of injuries in the hospital. The aide spoke on condition of anonymity because of fears of reprisals from the government.
The protests began with thousands of opposition supporters chanting "Death to the dictator," a reference to hard-line President Mahmoud Ahmadinejad, as they marched in defiance of official warnings of a harsh crackdown on any demonstrations coinciding with Ashoura. The observance commemorates 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, baton charges and warning shots. They then opened fire on protesters, killing at least three people, said witnesses and the Rah-e-Sabz Web site. Another 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.
An Iranian police statement said five people were killed in the unrest. "Experts are seeking to identify the suspicious elements," the statement said.
Iran's deputy police chief, Ahmad Reza Radan, said one person died after falling from a bridge, two were killed in a car accident, and a fourth was fatally shot.
"Given the fact that police did not use firearms, this incident looks completely suspicious and the case is under investigation," Radan said.
He said dozens of injured police were treated in hospitals, and more than 300 "seditionists" were arrested.
The clashes marked the bloodiest confrontation since the height of 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. Video footage circulating on the Web could also not be authenticated.
Ambulance sirens wailed near the site of the protests. Police helicopters circled as smoke billowed over the capital.
Cell phone services were unreliable and Internet connections were slowed to a crawl, as has happened during most other days of 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.
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.
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.
Foreign Minister Carl Bildt of Sweden, which holds the rotating presidency of the European Union, expressed concern about the "increased repression" in Iran.
"A regime secure in its own legitimacy has no reason to fear individuals' rights to express their opinions freely and peacefully," he wrote on his blog Sunday.