At least 15 Syrian children died in a suspected Russian air strike on a school in rebel-held territory near Damascus, while a surprise ISIL attack killed 36 pro-government fighters.
Two women were also killed in the air strike in the besieged Eastern Ghouta suburbs on the edge of the capital, a Britain-based war monitor said.
The Syrian Observatory for Human Rights said the bombing raid on Monday hit Arbin, a key town in the dwindling enclave that has been under attack by forces loyal to President Bashar Al Assad for more than a month.
"Three missiles from a single air strike hit the school, where the underground level was being used as a shelter," said Rami Abdel Rahman, who heads the monitor.
"Rescue workers are still searching for survivors."
The White Helmets rescue force was pulling bodies out of the rubble on Tuesday and said its workers had been directly targeted in continuous bombing that was complicating their operation.
The Observatory - which identifies air strikes based on flight patterns, munitions used and aircraft - said Russia was believed to have carried out the raid.
Moscow has said it is helping the Assad regime "finish off" fighters in Ghouta but has denied carrying out strikes against civilians.
The attack came as ISIL took control of a district on the outskirts of Damascus after their deadly attack on pro-Assad forces, following days of fighting.
"ISIL took full control of Qadam, and 36 government troops and loyalist fighters have been killed," said the Observatory, which could not provide casualty figures for the insurgents.
There was no immediate comment from the Assad government.
Mr Abdel Rahman said dozens more forces loyal to the Assad regime were wounded or captured, or are still missing in action.
He said ISIL launched the attack from positions it holds in the adjacent Hajar Al Aswad district.
"Regime forces are bringing reinforcements to the area around Qadam to try to retake it," Mr Abdel Rahman said.
Qadam lies in a southern part of Damascus and has for several years hosted a range of Islamist rebels and extremists, including ISIL and its rival, Al Qaeda's one-time Syrian branch Hayat Tahrir Al Sham.
The Syrian government has used both military pressure and negotiated settlements to try to clear the area.
Last week, hundreds of Hayat Tahrir Al Sham fighters left the district under a deal with the Assad regime that granted them and their family members safe passage. Most headed north-west to Idlib province.
But ISIL put out a statement late on Monday saying it had captured most of Qadam, including areas "surrendered" to regime forces by Hayat Tahrir Al Sham.
The district is smaller than and not connected to Eastern Ghouta.
On Tuesday, the Russian foreign ministry said that 79,702 civilians, most of whom are children, have been moved out of Eastern Ghouta as part of a humanitarian mission.
And it said in a statement posted on its website that on Monday alone, 6,046 civilians left the district via humanitarian corridors.
Since February 18, Syrian troops and allied militia have been waging a ferocious ground and air assault to flush out rebels from Ghouta, just east of Damascus.
They have captured more than 80 per cent of territory there and have splintered what remains into three sections, each held by a separate rebel group.
The pocket where Arbin lies is held by the Faylaq Al Rahman faction.
Syrian troops have made sweeping advances against them in recent days, opening a "corridor" for civilians to flee into government-controlled territory.
Other residents have opted to flee deeper into the shrinking rebel-held areas.
The White Helmets, who work to extract people after air strikes, said on Tuesday its teams in Arbin had come under fire.
"They're not able to use their heavy vehicles because the planes are targeting the Civil Defence directly," Oways Al Shami, a spokesman for the group, said of the rescuers.