A wave of air strikes and shelling have killed more than 60 people in less than 24 hours in the Syrian city of Aleppo, monitors and activists said.
The contested city is now one of the main battlegrounds of the country's devastating civil war, with a cease-fire that has collapsed and peace talks in Geneva stalled.
At least 27 people died as a hospital supported by Doctors Without Borders and the International Committee for the Red Cross (ICRC) and nearby buildings were hit overnight in the rebel-held part of Aleppo.
The UN envoy for Syria appealed early on Thursday to the US and Russia to help revive the peace talks and a cease-fire, which he said "hangs by a thread".
However, the violence only escalated. New air strikes in residential areas in the rebel-held part of the city killed at least 20 people while state media reported that at least 1,000 mortars and rockets were fired at government-held areas of Aleppo, killing at least 14 civilians.
Chief Syrian opposition negotiator Mohammed Alloush blamed the government of President Bashar Assad for the violence.
He said it shows "the environment is not conducive to any political action".
Around 200 civilians have been killed in the past week, nearly half of them around Aleppo.
There has also been shelling in Damascus, along with a car bombing - both rarities for the capital.
The ICRC said the fighting, including the destruction of the hospital, is putting millions at grave risk.
With peace talks in Geneva completely deadlocked, Syrians are regarding the escalating bloodshed with dread, fearing that Aleppo is likely to be the focus of the next phase of the war.
Rebel commanders said government forces have been mobilising soldiers, equipment and ammunition in preparation for a military action in Aleppo.
The well-known al-Quds hospital, supported by Doctors Without Borders and ICRC and located in the rebel-held district of Sukkari, was hit shortly before midnight on Wednesday, according to opposition activists and rescue workers.
Six hospital staff and three children were among the 27 who died there.
The Syrian Civil Defence, a volunteer first-responders agency whose members went to the scene of the attack, put the death toll at 30 and said the dead included six hospital staff.
Among those killed was one of the last paediatricians remaining in opposition-held areas of the city and a dentist.
The defence agency, also known as the White Helmets, said the hospital and adjacent buildings were struck in four consecutive air strikes.
It said some victims were still buried under the rubble and that the rescue work continued.
The Britain-based Syrian Observatory for Human Rights said three children were among the 27 victims but it was not immediately clear if they were patients at the hospital.
Doctors Without Borders, also known as MSF, said in a statement that at least 14 patients and staff were among those killed, with the toll expected to rise.
"Destroyed MSF-supported hospital in Aleppo was well known locally and hit by direct air strike," it said.
Muskilda Zancada, head of the MSF Syria mission, said: "This devastating attack has destroyed a vital hospital in Aleppo, and the main referral centre for paediatric care in the area.
"Where is the outrage among those with the power and obligation to stop this carnage?"
The 34-bed, multi-storey hospital had an emergency room and offered services such as obstetric care, outpatient and inpatient treatment.
It had an intensive care unit and an operating theatre. Eight doctors and 28 nurses worked full-time in the hospital, MSF said. It has supported the hospital since 2012.
A Syrian military official quoted on state TV denied reports that the hospital was targeted.
A video posted online by the White Helmets showed a number of lifeless bodies, including those of children, being pulled out from a building and loaded into ambulances amid screaming and crying.
It also showed distraught rescue workers trying to keep onlookers away from the scene, apparently fearing more air strikes.
Shortly after midday, new air strikes in rebel-held areas killed at least 20 people in two neighbourhoods, the Syrian Civil Defence and the Observatory said.
Videos provided by activists show scenes of dust rising up from buildings on fire as men and women run away from collapsing houses and children cry, looking for their parents.
In one clip, a man is seen lifting his daughter out of the rubble.
State media said at least 1,300 rockets and missiles fell in residential areas in government controlled parts of the city, killing 14 people on Thursday.
Mr Alloush, who was one of the leading negotiators of the opposition in the Geneva talks, described the air strikes as one of the latest "war crimes" of Mr Assad's government.
"Whoever carries out these massacres needs a war tribunal and a court of justice to be tried for his crimes. He does not need a negotiating table," he said.
"Now, the environment is not conducive for any political action."
The February 27 cease-fire has been fraying in the past weeks as casualty figures from violence mount, particularly in Aleppo and across northern Syria.
Air strikes earlier this week also targeted a training centre for the Syrian Civil Defence, leaving five of its team dead in rural Aleppo.
Nearly 200 people have died since April 19, including at least 44 in an air strike on a market place in rebel-held area in northern Idlib province, as well as dozens of civilians in government-held areas from rebel shelling.
The UN envoy for Syria, Staffan de Mistura, briefed the UN Security Council via video-conference about the largely stalled indirect talks between the Western- and Saudi-backed opposition and envoys from Mr Assad's government, which has the backing of Moscow.
He said that after 60 days, the cessation of hostilities agreed to by both sides "hangs by a thread".
"I really fear that the erosion of the cessation is unravelling the fragile consensus around a political solution, carefully built over the last year," Mr de Mistura said in his council briefing.
"Now I see parties reverting to the language of a military solution or military option. We must ensure that they do not see that as a solution or an option."
The talks foundered last week after the main opposition group, called the High Negotiating Committee, suspended its formal participation in the indirect talks with Mr Assad's envoys.
It is protesting against alleged government cease-fire violations, a drop in humanitarian aid deliveries and no progress in winning the release of detainees in Syria.