Sustained bursts of automatic weapons fire and powerful single shots rattled into the square starting at around 4 a.m. and continued for more than two hours.
Protest organizer Mustafa el-Naggar said he saw the bodies of three dead protesters being carried toward an ambulance. He said the gunfire came from at least three locations in the distance and that the Egyptian military, which has ringed the square with tank squads for days to try to keep some order, did not intervene.
Footage from AP Television News showed one tank spreading a thick smoke screen along a highway overpass just to the north of the square in an apparent attempt to deprive attackers of a high vantage point. The two sides seemed to be battling for control of the overpass, which leads to a main bridge over the Nile.
In the darkness, groups of men hurled firebombs and rocks along the bridge, where a wrecked car sat engulfed in flames. Others dragged two apparently lifeless bodies from the area.
Egypt's health minister did not answer a phone call seeking confirmation of the number killed.
Throughout Wednesday, Mubarak supporters charged into the square on horses and camels brandishing whips while others rained firebombs from rooftops in what appeared to be an orchestrated assault against protesters trying to topple Egypt's leader of 30 years. Three people died in that earlier violence and 600 were injured.
The protesters accused Mubarak's regime of unleashing a force of paid thugs and plainclothes police to crush their unprecedented nine-day-old movement, a day after the 82-year-old president refused to step down. They showed off police ID badges they said were wrested from their attackers. Some government workers said their employers ordered them into the streets.
Mustafa el-Fiqqi, a top official from the ruling National Democratic Party, told The Associated Press that businessmen connected to the ruling party were responsible for what happened.
The notion that the state may have coordinated violence against protesters, who had kept a peaceful vigil in Tahrir Square for five days, prompted a sharp rebuke from the Obama administration.
"If any of the violence is instigated by the government, it should stop immediately," said White House Press Secretary Robert Gibbs.
The clashes marked a dangerous new phase in Egypt's upheaval: the first significant violence between government supporters and opponents. The crisis took a sharp turn for the worse almost immediately after Mubarak rejected the calls for him to give up power or leave the country, stubbornly proclaiming he would die on Egyptian soil.
His words were a blow to the protesters. They also suggest that authorities want to turn back the clock to the tight state control enforced before the protests began.
Mubarak's supporters turned up on the streets Wednesday in significant numbers for the first time. Some were hostile to journalists and foreigners. Two Associated Press correspondents and several other journalists were roughed up in Cairo. State TV had reported that foreigners were caught distributing anti-Mubarak leaflets, apparently trying to depict the movement as foreign-fueled.
After midnight, 10 hours after the clashes began, the two sides were locked in a standoff at a street corner, with the anti-Mubarak protesters hunkered behind a line of metal sheets hurling firebombs back and forth with government backers on the rooftop above. The rain of bottles of flaming gasoline set nearby cars and wreckage on the sidewalk ablaze.
The scenes of mayhem were certain to add to the fear that is already running high in this capital of 18 million people after a weekend of looting and lawlessness and the escape of thousands of prisoners from jails in the chaos.
Soldiers surrounding Tahrir Square fired occasional shots in the air throughout the day but did not appear to otherwise intervene in the fierce clashes and no uniformed police were seen. Most of the troops took shelter behind or inside the armored vehicles and tanks stationed at the entrances to the square.
"Why don't you protect us?" some protesters shouted at the soldiers, who replied they did not have orders to do so and told people to go home.
"The army is neglectful. They let them in," said Emad Nafa, a 52-year-old among the protesters, who for days had showered the military with affection for its neutral stance.