A Syrian missile strike leveled a block of buildings in an impoverished district of Aleppo on Tuesday, killing at least 33 people, almost half of them children, anti-regime activists said.
Many were trapped under the rubble of destroyed houses and piles of concrete and the death toll could still rise further if more bodies are uncovered.
The apparent ground-to-ground missile attack struck a quiet area that has been held by anti-regime fighters for many months, a reminder of how difficult it is for the opposition to defend territory in the face of the regime's far superior weaponry.
In the capital Damascus, state-run news agency SANA said two mortars exploded near one of President Bashar Assad's palaces. It dealt a symbolic blow to the embattled leader, who has tried to maintain an image as the head of a functioning state even as rebels edge closer to the heart of his seat of power.
No casualties were reported and it was unclear whether Assad was in the palace. He has two others in the city.
The attack was the first confirmed strike close to a presidential palace and another sign that the civil war is seeping into areas of the capital once considered safe.
"This is a clear message to the regime that nowhere is safe from now on," said Khaled al-Shami, an activist in Damascus reached via Skype. "The fact that they had to announce it means they can no longer hide what is happening in Damascus."
The news service, SANA, said "terrorists" fired the rounds that struck near the southern wall of the Tishreen palace in the capital's northwestern Muhajireen district. The government refers to anti-government fighters as "terrorists."
Assad often uses the Tishrin palace to receive dignitaries and as a guest house for foreign officials during their visits to Syria.
The capital has largely been spared the violence that has left other cities in ruins. For weeks, however, rebels who have established footholds in the suburbs have been pushing closer to the heart of Damascus from the eastern and southern outskirts, clashing with government forces.
Rebels have claimed to fire rockets at presidential palaces in Damascus before, but this strike was the first confirmed by the government.
In the northern city of Aleppo, anti-regime activists said a missile strike flattened a stretch of buildings and killed at least 33 people. The Britain-based Syrian Observatory for Human Rights said they included 14 children and five women.
Amateur videos posted online showed scores of men combing through the rubble of destroyed buildings in the poor Jabal Badro neighborhood to find those trapped beneath it.
"Allahu Akbar," or God is great, they shout as a group of men lift up a body wrapped in a pink blanket.
One man swung a sledgehammer to break through concrete while a bulldozer hauled off rubble. In another video, a man covered in grey dust struggled under pile of concrete.
The videos appeared authentic and corresponded with other Associated Press reporting.
The Jabal Badro district has been under rebel control for months and had been largely quiet until Tuesday's attack.
The strike was the latest salvo in a fierce and bloody 7-month battle for Syria's largest city and economic center, a key prize in the civil war.
Rebels have slowly expanded their control over parts of Aleppo since first storming it last summer. The city is now divided between rebel- and regime-controlled zones.
Rebel forces have been trying for weeks to capture Aleppo's international airport and two military air bases nearby, while the government is bringing in reinforcements from areas it still controls further south and regularly bombing rebel areas from the air.
The activist group Aleppo Media Center said more than 40 were killed and published the names of 21 off them on its Facebook page. There was no way to reconcile the differing tolls.
Both the Observatory and AMC groups said the strike appeared to be from a ground-to-ground missile. The Syrian government did not comment.
Activist Mohammed al-Khatib of the AMC said via Skype that the death toll could rise further as residents search the site for more bodies.
"There are still lots of people missing from the area," he said.
He said the strike appeared to be from a large ground-to-ground missile because of the scale of the destruction and because residents did not report hearing a fighter jet, as they usually do during airstrikes.
Although Assad's forces regularly shell and launch airstrikes on areas held by anti-government rebels, their use of large missiles has been limited.
In December, U.S. and NATO officials confirmed rebel reports that Syrian forces had fired Scud missiles at rebel areas in the north. That was the last confirmed use of such weapons.
Also Tuesday, rebels clashed with government forces near Aleppo's international airport and the Kweiras military airport nearby, the Observatory said. Clashes have halted air traffic to the two airports for weeks, since rebels launched their offensive to try to capture them.
The Observatory also reported government shelling, airstrikes and clashes between government forces and rebels east and south of Damascus.
Seven people were killed in rocket strikes on the eastern suburb of Kafar Batna and five died in a car bombing in Jdeidat al-Fadel, southwest of the capital, it said.
The U.N. says some 70,000 have been killed since the uprising against Assad's authoritarian rule began in March 2011. The violence has spread humanitarian suffering across much of Syria.
U.N. humanitarian chief Valerie Amos said the number of people in need of humanitarian assistance has quadrupled since June last year.
"Just in the last two months, over 250,000 people have fled into neighboring countries. These numbers, they are not sustainable," she said at a press conference in Geneva.
The U.N. says more than 870,000 Syrians have fled to neighboring countries since the beginning of the conflict, with the majority seeking refuge in Jordan, Turkey and Lebanon.
The United States announced Tuesday it was providing an addition $19 million in humanitarian assistance in response to urgent needs in Syria.
The announcement made in Geneva by Nancy Lindborg, assistant administrator for the U.S. Agency for International Development, brings the United States' total contribution of humanitarian support in response to this crisis to nearly $385 million.
On January 29, President Barack Obama announced an additional $155 million to help those suffering inside Syria and refugees in the neighboring countries.
The U.N. warned in a report released Monday that contaminated water and poor hygiene in populated areas have led to an increase in waterborne diseases such as Hepatitis A and Typhoid.
The World Health Organization said the health situation on the ground is rapidly deteriorating, with an estimated 2,500 people in the northeastern Deir el-Zour province infected with Typhoid and 14,000 cases of Leishmania, a parasite responsible for an infectious and often debilitating disease, in Hassakeh province.
Associated Press writers Albert Aji in Damascus, Bassem Mroue and Ben Hubbard in Beirut, Frank Jordan in Berlin and Nataliya Vasilyeva in Moscow contributed reporting.