US-led coalition air strikes killed nearly 60 people at a Syrian prison run by the Islamic State group, a monitor said Tuesday, as critics hit out at Washington for threatening action against Damascus.
The coalition has been striking IS in Syria and Iraq since mid-2014 but has also been involved in recent confrontations with President Bashar al-Assad's forces, raising fears of the United States being drawn into Syria's civil war.
The White House on Monday accused Assad's regime of preparing a potential chemical attack and said it would pay a "heavy price", prompting criticism from regime allies Russia and Iran.
Monday's strikes hit an IS-run jail in Syria's Mayadeen at dawn, according to the Syrian Observatory for Human Rights, a Britain-based war monitor.
Observatory chief Rami Abdel Rahman told AFP the strikes killed 42 prisoners and 15 jihadists in Mayadeen, a large town in the eastern province of Deir Ezzor.
Pentagon spokesman Adrian Rankine-Galloway confirmed coalition strikes on Mayadeen on Sunday and Monday, targeting IS "command and control facilities" and other "infrastructure".
The allegations of casualties at the prison "will be provided to our civilian casualty team for assessment," he added.
Most of Deir Ezzor province is controlled by the jihadists and it has been the target of air strikes by both the coalition and the Syrian army and its Russian ally.
The jihadists, who seized control of large parts of Syria and Iraq three years ago, are under pressure in both countries.
US-backed forces are pushing to oust IS, also known as ISIS and ISIL, from its last major urban strongholds, Raqa in Syria and Mosul in Iraq.
But the US involvement in Syria has also become increasingly complex.
On Monday the White House said preparations were underway by the regime for a chemical weapons attack, similar to those undertaken ahead of an apparent gas attack on a rebel-held town in April.
"If... Mr Assad conducts another mass murder attack using chemical weapons, he and his military will pay a heavy price," White House spokesman Sean Spicer said in a statement.
April's attack on the rebel-held town of Khan Sheikhun was reported to have killed at least 87 people, including many children, and images of the dead and of suffering victims provoked global outrage.
The regime denied any use of chemical weapons.
Washington launched a retaliatory cruise missile strike days later against Syria's Shayrat airbase from where it said the chemical attack was launched, the first direct US action against the regime.
Pentagon spokesman Navy Captain Jeff Davis said Tuesday the latest US warning was the result of activity at the same airbase "that indicated preparations for possible use of chemical weapons".
The White House statement drew condemnation from Moscow, with Kremlin spokesman Dmitry Peskov telling journalists: "We consider such threats against the Syrian leadership to be unacceptable."
Iran also warned the United States.
"Another dangerous US escalation in Syria on fake pretext will only serve ISIS, precisely when it's being wiped out by Iraqi and Syrian people," Foreign Minister Mohammad Javad Zarif tweeted.
Defence Secretary Jim Mattis insisted the United States was not taking sides in the Syrian conflict.
US forces would not fire on targets "unless they are the enemy, unless they are ISIS," he said late on Monday.
"We just refuse to get drawn into a fight there in the Syria civil war, we try to end that one through diplomatic engagement."
Coalition forces on the ground have accused pro-regime fighters of targeting them in recent weeks, as they shot down two Iran-made attack drones and a Syrian fighter jet.
The Pentagon chief highlighted the importance of maintaining communication with Russia, which is also backing Assad's forces with air strikes.
Assad on Tuesday toured the airbase in western Syria set up for the Russian intervention, inspecting equipment and even climbing into the cockpit of a Sukhoi fighter jet.
"The Syrian people will not forget the support of their Russian brothers," Assad wrote in the visitors' book at the Hmeimim base.
The Russian intervention marked a major turning point in the conflict and pro-regime forces have since made significant gains, including their recapture of second city Aleppo.