"At least 34 people were killed in Hama by security forces but the toll could rise as there are people who were gravely wounded," said Rami Abdel Rahman who heads the London-based Syrian observatory for human rights.
Security forces unleashed "intense gunfire" against a crowd of more than 50,000 people in Hama, Abdel Rahman said, reached by telephone from Nicosia.
He said the rally was the biggest in the city since the mid-March outbreak of a revolt against Syrian President Bashar al-Assad's autocratic rule.
Other activists in Hama told AFP by telephone that dozens of other people were wounded.
Elsewhere, security forces killed one civilian when they opened fire to disperse a protest in the village of Has in the province of Idlib, Abdel Rahman said.
"Today's demonstrations are the largest yet since the start of the protest movement and come despite the general amnesty" for political prisoners announced by Assad on Wednesday, said Abdel Rahman.
"This shows the people no longer trust the regime," he said.
The official SANA news agency said "three saboteurs where killed in clashes with police after they attacked and set fire to a government building" in Hama, giving a crowd estimate of "hundreds."
It said 80 security force members were injured in Hama.
State television said late Friday that calm was returning to Hama after armed groups, taking advantage of a crowd of "nearly 10,000" opened fire on civilians and the security forces.
In 1982, Hama was the scene of a brutal crackdown that left an estimated 20,000 people dead when the Muslim Brotherhood rose up against the late Hafez al-Assad, father of the current Syrian president.
Thousands of demonstrators on Friday also rallied in and around Damascus, which so far has been largely spared the protests rocking Syria for more than 10 weeks, another rights activist said.
In the central city of Homs, around 50,000 people staged a protest after the weekly Friday prayers, according to activists reached by telephone.
Near the southern protest hub of Daraa, security forces opened fire to disperse a crowd in Jassem, a rights activist told AFP, as protesters also gathered in nearby Dal and in Kurdish towns of northern Syria.
Overnight, in several cities including Aleppo in the north and Deir Ezzor in eastern Syria residents took to rooftops to chant "God is greatest," a slogan taken up by the opposition, said Abdel Rahman.
State television said that two security force members were killed in clashes -- one in Damascus and one in Deir Ezzor.
UN chief Ban Ki-moon meanwhile was "deeply troubled by the continued serious violations of human rights, including disturbing reports of the deaths of children under torture, live ammunition and shelling" in Syria, a UN spokeswoman, Vannina Maestracci, said in New York.
"The secretary general is alarmed at the escalation of violence in Syria, which has reportedly left at least 70 killed over the past week alone, bringing the total casualties since mid-March to over 1,000 dead, many more injured and thousands arrested," she said.
It was the first death toll from the protests given by the UN leadership.
Rights groups say more than 1,100 civilians have been killed and at least 10,000 arrested in a brutal crackdown on almost daily anti-regime demonstrations in Syria since March 15.
Residents, meanwhile, said Internet lines were cut in Damascus and the coastal city of Latakia on Friday, in a repeat of a suspension of services at the start of April.
US monitoring group Renesys, which monitors Internet routing data in real-time, said in a blog post that beginning at 0335 GMT the routes to 40 of 59 networks became unreachable over the course of half an hour.
Syrian activists called the latest protests over the dozens of children killed in anti-government protests such as 13-year-old Hamza al-Khatib whom activists say was tortured to death, a charge denied by the authorities.
The government insists the unrest in Syria is the work of "armed terrorist gangs" backed by Islamists and foreign agitators.
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