TEHRAN, Iran — Witnesses said police beat protesters and fired tear gas and water cannons at thousands who rallied in Tehran Saturday in open defiance of Iran's clerical government, sharply escalating the most serious internal conflict since the 1979 Islamic Revolution.

The eyewitnesses described fierce clashes near Revolution Square in central Tehran after some 3,000 protesters chanted "Death to the dictator!" and "Death to dictatorship!" Police responded with tear gas and water cannons.

The witnesses told The Associated Press that between 50 and 60 protesters were seriously beaten by police and pro-government militia and taken to Imam Khomeini hospital in central Tehran. People could be seen dragging away comrades bloodied by baton strikes.

Helicopters hovered over central Tehran. Ambulance sirens echoed through the streets and black smoke rose over the city.

Tehran University was cordoned off by police and militia while students inside the university chanted "death to the dictator," witnesses said.

English-language state TV said a blast at the Tehran shrine of Ayatollah Ruhollah Khomeini had killed one persona and wounded two but the report could not be independently confirmed due to government restrictions on independent reporting.

Supreme Leader Ayatollah Ali Khamenei warned opposition leaders on Friday to end street protests or be held responsible for any "bloodshed and chaos" to come.