Websites affiliated with the Syrian opposition said some 300 people were injured in the demonstration and that local hospitals were unable to take in such a large number of patients.
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Tens of thousands of protestors took to the streets of Hama, located some 300 kilometers (186 miles) north Damascus. As they marched near the city's old quarter, security forces opened fire.
It was one of the biggest demonstrations in the country since the uprising against President Bashar Assad began in March.
Opposition websites reported of dozens of dead bodies scattered on the city's streets on Friday evening. Some of the bodies were loaded on cars and others were evacuated to apartment buildings until they would be taken care of. This report has not been confirmed by any other source.
The opposition websites also reported that thousands of Homs residents took to the streets after learning of the killings in Hama, adding that the security forces were forced to withdraw from the streets.
Another unusual sight came from the southern city of Daraa, where protestors set fire to the flags of Iran, China and Russia – countries they say have been backing Assad. "Syria is free, the traitor must leave," they chanted.
Protests were also reported Friday evening in some of the quarters of Aleppo, Syria's second biggest city, following the bloody clashes in Hama.
The French news agency defined Friday's protests in Syria as "the largest anti-regime demonstrations yet".
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.
Syrian human rights organizations say at least 30 children have been shot dead in the revolt against Assad's autocratic rule.
UN chief: End 'violent repression' now
The United Nations chief on Friday demanded an immediate end to the "violent repression" and human rights abuses by Syrian forces in their bloody crackdown against anti-government protesters.
Secretary-General Ban Ki-moon "is deeply troubled by the continued serious violations of human rights, including disturbing reports of the deaths of children under torture, live ammunition and shelling," UN spokeswoman Vannina Maestracci told reporters.
She said Ban "takes note" of a promised amnesty and call for national dialogue by the Syrian authorities.
"He emphasizes, however, that violent repression by security and military forces must end immediately for a genuine and inclusive dialogue to take place and lead to the comprehensive reforms and change called for by the Syrian people," Maestracci said.
She added that Ban reiterated his for call for a full, transparent and independent investigation into the killings.
The UN Security Council is considering a draft resolution condemning Syria which was circulated to its 15 members by Britain, France, Germany and Portugal last week. Veto powers Russia and China have made clear they dislike the idea of council involvement in what they see as a domestic issue.
Diplomats said Security Council envoys met on Thursday to see if there was any way to amend the resolution so that Russia and China would not veto it. They have yet to overcome their differences, Western diplomats said.
Reuters and AFP contributed to this report
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