A protest by about 350,000 Ukrainians, angered by their government's decision to freeze integration with the West, turned violent when a group of demonstrators besieged the president's office and police drove them back with truncheons, tear gas and flash grenades, according to the Reuters news agency.
Chants of "revolution'' had earlier resounded across a sea of European Union and Ukrainian flags at the square, where the government had banned rallies starting Sunday. The standoff continued, with more demonstrators arriving.
The crowd was by far the largest since the protests began more than a week ago. Many of the demonstrators had traveled to Kiev from western Ukraine, where pro-EU sentiment is particularly strong.
The protest was led by prominent opposition politicians, who demanded that President Viktor Yanukovych and his government resign. They also called for a nationwide strike and for tents to be set up to allow demonstrators to remain on the square around the clock.
"Our plan is clear: It's not a demonstration, it's not a reaction. It's a revolution," said Yuriy Lutsenko, speaking from the top of a bus.
On a day of intense emotion, which also marked the anniversary of Ukraine's 1991 referendum on independence from the former Soviet Union, opposition leaders denounced Yanukovich for walking away from a pact offered by the EU and swinging trade policy back toward Russia.
"They stole the dream," heavyweight boxer-turned-opposition politician Vitaly Klitschko told the crowds at Independence Square.
"If this government does not want to fulfill the will of the people, then there will be no such government, there will be no such president. There will be a new government and a new president," declared Klitschko, a contender for the next presidential election due in 2015.
After months of pressure from Russia, Yanukovich suddenly backpedalled from signing the deal on closer relations with the EU in favor of renewed economic dialogue with Moscow, Ukraine's former Soviet master.
Far-right nationalist leader Oleh Tyahniboh called for a national strike, and members of his Svoboda (Freedom) party occupied Kiev's city hall along with followers of former economy minister Arseny Yatsenuk's Batkivshchyna (Fatherland) Party.
"From this day, we are starting a strike," he declared. Backing for a national strike may indicate the protests' staying power in the coming days. All three opposition leaders also occupied a trade union building, turning it into a temporary headquarters.
The events, evoking memories of the 2004-05 Orange Revolution that overturned the established political order, took place against the background of an apparent attempt by protesters to storm the main presidential office.
Interior Ministry forces and riot police kept the protesters – who used an excavator in an attempt to break through police lines – at bay.
Police said 100 officers had been injured in violence during the day, news agencies reported.
"We are furious," said Mykola Sapronov, a 62-year-old retired businessman. "The leaders must resign. We want Europe and freedom."
Protests have been held daily in Kiev since Yanukovych backed away from an agreement that would have established free trade and deepened political cooperation between Ukraine and the EU. He justified the decision by saying that Ukraine could not afford to break trade ties with Russia.
Sunday's demonstration was also energized by anger over the violent dispersal of several hundred protesters at Independence Square early Saturday. Some of the protesters were left bleeding from their heads after riot police beat them with truncheons.
"They want to take our freedom away from us," said Nina Moskalik, 25. "They beat people, they spill blood. This is why we have to come out."
Yanukovych late Saturday condemned the use of force and promised to punish those responsible.
Al Jazeera and Wire Services