At least 42 people have died after the Syrian army stormed Deir al-Zour, the largest city in the east and a scene of frequent protests, activists say.
Scores of tanks and armoured vehicles are reported to have entered several areas of the city after a heavy bombardment that began before dawn.At least 13 other people have been killed in Homs province and six in Idlib in the north-west, activists say.
President Bashar al-Assad has defended his security forces' deadly crackdown.
"Syria is on the path to reform," he was quoted as telling Lebanese Foreign Minister Adnan Mansour by the state news agency, Sana.
"To deal with outlaws who cut off roads, seal towns and terrorise residents is a duty of the state, which must defend security and protect the lives of civilians," he added.
Mr Assad's comments came after UN Secretary General Ban Ki-moon urged him to stop the use of military force against civilians immediately.
In a telephone call on Saturday, Mr Ban "expressed his strong concern and that of the international community at the mounting violence and death toll in Syria over the past days", a UN spokesman said.
It was the first such communication in several months; the UN says Mr Assad had been refusing to accept calls from the secretary general.
Activists say at least 1,650 civilians have been killed and tens of thousands arrested since the uprising began in mid-March.
Access to Syria has been severely restricted for international journalists and it is rarely possible to verify accounts by witnesses and activists.
City 'totally paralysed' Activists said the bombardment of Deir al-Zour, about 450km (280 miles) east of Damascus, began at dawn on Sunday, with scores of tanks and armoured personnel carriers moving into many parts of the city, to the sound of loud explosions and machine-gun fire.
Residents of the city of Deir al-Zour had been expecting a military operation and many of them had fled in the last week.
Deir al-Zour is the second city to see huge protests. Almost 400,000 people are said to have been taking to the streets every Friday. This is something the regime won't tolerate.
After similar demonstrations in Hama, the authorities seem to be warning the rest of the country by attacking another city which dares to challenge the power of President Assad.
Pressure from the United Nations and the international community doesn't seem to he having an effect. The crackdown has expanded to include prominent opposition figures like former political prisoner Walid al-Bunni who was detained along with his two sons. A sign that things could get even worse in coming days.
"We are surrounded by military forces, security apparatus and government thugs," one resident told the BBC World Service. "They were firing randomly at people up until 15 minutes ago. The gunfire was very heavy on al-Wadi Street."
He said there were no protests taking place in the city, but that government forces had threatened to attack hospitals and ambulances.The wounded were treated by field clinics set up inside mosques. Some bodies were buried in a park as it was not possible to get to the cemetery, residents said.
The Local Co-ordination Committees, an activist group that documents and organises protests, said nine districts had been stormed, but that the gunfire and casualties were heaviest in al-Joura, where snipers occupied the rooftops of most of the area's high buildings.
Activists said people were unable to flee because troops were all around, but also that some of the soldiers in al-Joura had defected rather than shoot at people. Some began trying to protect civilians, they added.
The national Syrian Revolution Co-ordination Committee said the number of people killed in Deir el-Zour had reached at least 50.
"The numbers of casualties are escalating by the hour," said committee member Suhair al-Atassi.
Earlier this week, residents had reported the build-up of soldiers and tanks, which they said were trying to divide the city into smaller parts.
State media said local leaders had called on the army to enter Deir al-Zour "to protect the citizens and preserve the public and private properties".
Parts of the city were shelled on Thursday night and Friday morning, witnesses said. Some reported shortages of food and water.
"Conditions in the city are very bad since it has been under siege for nine days," one activist told the Associated Press. "There is lack of medicine, baby formula, food stuff and gasoline. The city is totally paralysed."
Despite the imminent threat of an assault, tens of thousands of demonstrators took to the streets on Friday, chanting: "We don't want the army inside the cities".
The BBC's Jim Muir in Beirut says Deir al-Zour, on the Euphrates river and not far from the border with Iraq, is in a strongly tribal area. Some tribal leaders have declared loyalty to the regime, but not all.
'Excess force' Activists also said security forces backed by tanks had killed at least 13 civilians, including a 10-year-old boy, and wounded several others on Sunday in the village of Hula, 30 km (19 miles) north of the city of Homs. The Syrian Revolution Co-ordination Committee put the number of victims in Hula at 21.
The army has continued its siege on the central city of Hama, which has become the centre of the uprising. Earlier, the Local Co-ordination Committees said the number of those killed since security forces launched an assault last Sunday was now more than 300.
Syrian uprising: Deadliest days
18 Mar Unrest in Deraa triggers nationwide anti-government protests22 Apr: 82 killed around the country as tens of thousands pour onto streets
29 Apr: 62 killed nationwide, including 33 in Deraa
3 Jun: More than 60 killed at Hama demonstration
6 Jun: Government says 120 security forces personnel killed in Jisr al-Shughour
21 Jul: At least 50 killed in Homs as army is sent to crush dissent
31 Jul: More than 130 killed nationwide as tanks storm centres of unrest; dozens killed in Hama
3 Aug: At least 45 killed in Hama as security forces try to regain control of city
7 Aug: 42 killed in Deir al-Zour and 13 in Hula as army launches assaults
Sources: Human rights and opposition activists
The crackdown is going ahead despite mounting appeals, condemnation and pressure from outside the country.
In its first comments about the unrest, the six-nation Gulf Co-operation Council on Saturday condemned "the escalating violence in Syria and use of excess force" and called for an "immediate end to the violence and any armed appearances, as well as an end to the bloodshed".The Arab League also issued a statement expressing "growing concern and strong distress over the deteriorating security conditions in Syria due to escalating violence and military operations in Hama and Deir al-Zour and other areas of Syria", Qatar's state news agency QNA reported.
Diplomatic tension with neighbouring Turkey seems to be rising, our correspondent says.
Prime Minister Recep Tayyip Erdogan said Ankara had "run out of patience" with Mr Assad's regime and that it could no longer "remain a spectator" to events across its border.
He announced he was sending Foreign Minister Ahmet Davutoglu to Damascus on Tuesday with a tough message, our correspondent adds, but one of Mr Assad's top advisers said he would be given an even tougher message to take home.
The US ambassador to Syria, Robert Ford, has said Washington also intends to "ratchet up the pressure" on the regime.
Mr Ford, who left Syria after angering the regime by taking part in a protest in Hama last month, told ABC News he was returning as it was "important to bear witness to what the Syrian government is doing".
Meanwhile, Syrian Foreign Minister Walid Muallem said the government would hold "free and transparent" elections before the end of 2011, which would "give birth to a parliament representing the aspirations of the Syrian people".
Later, security forces had arrested the prominent opposition figure and former political prisoner, Walid al-Bunni, and his two sons, activists said. Four activist brothers from the Khattab family were also detained.
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