Activists said security forces killed at least two people and wounded 12 others in the central city of Homs, where more than 100,000 people defied the government crackdown.
Agence France Presse quoted an activist from Homs saying: “Two demonstrators died from firing by the security forces in the districts of Bab Sebaa and Al-Qarabis. Twelve others were wounded in various other areas of the city.”
Another demonstrator was also reportedly killed in Qadam, a suburb of the capital Damascus.
Al-Jazeera reported that soldiers, backed by armoured vehicles, had been setting up road blocks on the main roads in the city to prevent the protests.
Protests were also said to have taken place in eastern and western cities and in towns along the border regions, while the London-based Syrian Observatory for Human Rights says explosions were heard in Latakia.
Abdel Karim Rihawi, president of the Syrian League for Human Rights told AFP by telephone that in Hama, 210 kilometres north of Damascus, more than 200,000 protesters gathered in Al-Assi Square after Friday prayers.
The protests came as US Secretary of State Hillary Clinton told a democracy conference in Lithuania that the clock was ticking for Assad, who would continue to see “increasingly organised resistance” to his crackdown.
Friday's protests followed a call from a Facebook group for people to take to the streets nationwide.
The Syrian Revolution 2011 group called on people to rally after weekly prayers, branding July 1 “the Friday of departure”.
Rights campaigners say more than 1,300 activists have been killed in Syria since protests erupted in March.