The United States said Wednesday it was "horrified" by Syrian regime air strikes in the stronghold Raqa that killed at least 95 people, slamming the government for its "continued slaughter."
The bombing Tuesday was the deadliest by President Bashar al-Assad's air force since Islamic State jihadists seized the city last year and declared it their capital.
It was not clear how many Islamic States members were killed, but the Syrian Observatory for Human Rights said more than half of the dead were civilians.
The US State Department condemned the strikes, and said the regime had no value for human life.
"We are horrified by the reports that the Assad regime's airstrikes yesterday in Raqa, Syria killed dozens of civilians and demolished residential areas," State Department spokeswoman Jen Psaki said in a statement.
"The Assad regime's continued slaughter of Syrian civilians further exposes its callous disregard for human life."
She said Assad had lost his right to rule, and said his actions should be held accountable.
"We've been clear that Assad long ago lost all legitimacy to govern and that the Syrian regime must be held responsible for its brutality and atrocities against the Syrian people."
Psaki blamed Assad's government for continued human rights abuses and violating international law, accusing the regime of "murder, hostage-taking, enforced disappearances, torture, rape, sexual violence and the indiscriminate use of barrel bombs."
The United States has built up a coalition of more than 60 countries in the fight against the Islamic States militants who have seized swathes of territory in Iraq and Syria.
US President Barack Obama has rejected an alliance with Assad against the Islamic State group, arguing that any such pact would backfire.
Obama has said communication with the Assad regime was limited to informing them when they use Syrian air space in operations against the Islamic State jihadists.