Syrian security forces have used tear gas and batons to disperse tens of thousands of protesters in the capital, Damascus, witnesses said.
The protesters called for reforms, while some demanded the overthrow of President Bashar al-Assad.
The protests, in Damascus and other cities, are believed to be the largest in a month of unrest in which about 200 people have been reported killed.
Mr Assad has made some concessions while cracking down on dissent.
Thousands of people were reported to have demonstrated in a number of other Syrian cities, including Deraa, Latakia, Baniyas and Qamishli - places where violence has been previously reported.
State media reported that "small demonstrations" had taken place in different parts of the country and security forces did not intervene.
Yellow card warning
The mass protest in the suburbs of Damascus marks a major escalation of Syria's month of unrest, which has largely bypassed the capital.
Analysts said Friday's protests were the largest since they began in the southern city of Deraa on 15 March.
The unrest is seen as the biggest challenge to Mr Assad, who inherited power from his father in 2000.
The protesters say they want greater freedoms, including a repeal of the decades-old security law, which bans public gatherings of more than five people.
Some are calling for the overthrow of the president, who rules with a tight grip through his family and the security forces.
Mr Assad has offered some concessions, forming a new government on Thursday and pronouncing amnesty for an undisclosed number of people detained in the last month.
He has also sacked some local officials and granted Syrian citizenship to thousands of the country's Kurdish minority - satisfying a long-held demand.
The demonstrators in Damascus held up yellow cards, in a football-style warning to President Assad, AP news agency said.
"This is our first warning, next time we will come with the red cards," one protester said.
Other witnesses said the demonstrators tore down posters of Mr Assad they passed along their route and called for the overthrow of the president.
Reuters quoted a witness who said 15 busloads of secret police had chased people into alleyways north of the city's main Abbasside Square.
The United Nations and a number of Western governments have decried President Assad's use of force to try to quash the protests.
US Secretary of State Hillary Clinton called on Syria's authorities to stop using violence against their own people.
"The Syrian government has not addressed the legitimate demands of the Syrian people," she said after a Nato meeting in Berlin.
"It is time for the Syrian government to stop repressing their citizens and start responding to their aspirations."
Human rights campaigners say hundreds of people across Syria have been arrested, including opposition figures, bloggers and activists.
Mr Assad blames the violence in recent weeks on armed gangs rather than reform-seekers and has vowed to put down further unrest.
US officials have said Iran is helping Syria to crack down on the protests, a charge both Tehran and Damascus have denied.