People took the streets in the capital, Damascus, and in several cities and towns, in what the opposition described as the biggest demonstrations yet.
US Secretary of State Hillary Clinton has warned that time is running out for Syria's government to usher in reforms.
Speaking during a visit to Lithuania, she said President Bashar al-Assad would face more organised resistance to his 10-year rule unless the country saw "a genuine transition to democracy".
Human rights groups say more than 1,350 civilians and 350 security personnel have been killed since protests began in mid-March.
The government has blamed the protests on armed gangs.
Mr Assad has promised a national dialogue on political reforms, but many protesters are demanding that he stand down immediately.
'God, Syria, Bashar' Hundreds of thousands of people attended demonstrations across Syria after Friday prayers. Some activists put the number of protesters at three million.
Hama residentHundreds of thousands are chanting 'Leave, leave, the people want the fall of the regime.' All of Hama is celebrating”
About half a million were said to have joined the largest protest, in the central city of Hama, though that figure could not be confirmed.One Hama resident told the BBC Arabic: "Hundreds of thousands are chanting 'Leave, leave, the people want the fall of the regime.'"
"All of Hama is celebrating. There are people chanting from their windows and from the fronts of their homes. All of Hama is on the streets today."
Hama was the scene of a brutal crackdown in 1982 ordered by Hafez al-Assad, the president's late father, which left at least 10,000 dead.
In Homs, to the south of Hama, six people were reportedly shot dead and several injured as government troops fired on protesters - armoured vehicles were deployed in the Bab Amr district of the city, activists said.
Two people were reportedly killed during a protest in the Damascus suburb of al-Qadam. Six others were killed in the north-western Idlib province, Darayya, outside Damascus, and also in the coastal town of Latakia, the activists added.
State television gave a different death toll, saying gunmen had killed one person in Damascus and two people in Homs, including a policeman.
The figures could be independently verified as the Syrian authorities have banned most foreign media from the country.
Protests were also staged in Syria's second-largest city, Aleppo, where police fired tear gas, in the eastern city of Deir al-Zour, the north-eastern town of Amouda, and the southern town of Suweida.
State TV aired images of pro-government rallies in Aleppo It showed people waving national flags and chanting "God, Syria, Bashar, only."
'Genuine transition' The Syrian Revolution 2011 group on Facebook had called on protesters to turn out after Friday prayers, with the message to Mr Assad: "We don't love you... Go away, you and your party."
Pro-government demonstrations were also held in Damascus and several other towns on Friday, with marchers saying they backed Mr Assad's pledges to reform.
The latest anti-Assad protests follow the death of three more people overnight in the north-western region of Jabal al-Zawiyah, activists said - two in the town of al-Bara and one in the nearby village of Brim.
AFP also quoted activists as saying there had been explosions on Friday in the coastal city of Latakia.
Speaking earlier on Friday, Mrs Clinton said the Syrian authorities "know what they have to do".
"They must begin a genuine transition to democracy and allowing one meeting of the opposition in Damascus is not sufficient action toward achieving that goal," she said.
''It is absolutely clear that the Syrian government is running out of time.
"They are either going to allow a serious political process that will include peaceful protests to take place throughout Syria and engage in a productive dialogue with members of the opposition and civil society, or they're going to continue to see increasingly organised resistance."