The Syrian government has "categorically" denied US accusations of mass killings at a prison near Damascus, including executing political opponents and burning the victims in a crematorium at the site.
The Foreign Ministry said the allegations are a "new Hollywood plot" to justify US intervention in Syria.
It described the allegations as "lies" and "fabrications", noting what it called a US track record of using false claims as a pretext for military aggression.
The State Department said it believes about 50 detainees are being hanged each day at the Saydnaya military prison, a 45-minute drive north of Damascus.
Many of the bodies are then burned in the crematorium "to cover up the extent of mass murders taking place", said Stuart Jones, the senior US diplomat for the Middle East, accusing President Bashar Assad's government of sinking "to a new level of depravity".
The allegation came as President Donald Trump weighs options in Syria, where the US launched cruise missiles on a government air base last month after accusing Assad's military of killing scores of civilians with a sarin-like nerve agent.
The latest accusations have cast a shadow over peace talks in Geneva, where Syrian government and opposition representatives sat down separately with the UN envoy as talks got under way.
The meetings were the sixth round of talks brokered by special envoy Staffan de Mistura.
The Syrian Foreign Ministry said: "The US administration's accusations against the Syrian government of a so-called crematorium in Saydnaya prison, in addition to the broken record about the use of barrel bombs and chemical weapons, are categorically false."
The allegation could test the Trump administration's willingness to respond to alleged atrocities other than chemical weapons attacks, which Washington blames on Assad's government.
Western monitors and watchdog groups say they have evidence of mass killings in Syrian government prisons, although there have been no substantiated allegations on the use of a crematorium.
Syrian opposition spokesman Salem Meslet said the US allegations were "credible" and not surprising.
Mr Meslet, in Geneva for the UN-mediated talks, told Saudi-owned TV station al-Hadath that the government was known to move prisoners from site to site for interrogations and, in some instances, executions.
The US State Department released commercial satellite photographs showing what it described as a building in the prison complex that was modified to support the crematorium. The photographs, taken over the course of several years, beginning in 2013, do not prove the building is a crematorium, but show construction consistent with such use.
The revelations echoed a February report by Amnesty International that said Syria's military police hanged as many as 13,000 people in four years before carting out bodies by the truckload for burial in mass graves.
Meanwhile, Syrian activists said government forces were escalating attacks on opposition-held areas protected under a recently brokered ceasefire.
The Britain-based Syrian Observatory for Human Rights said it had recorded the first fatalities inside the country's four "de-escalation zones" since the agreement came into effect 10 days ago. The deal was brokered by Russia, Turkey and Iran.
The Observatory said two women were killed by rocket fire in a Damascus suburb and another was killed in aerial bombardment in central Homs province.
Local activists reported higher death tolls. Wael Abou Rayan, a media activist in the Homs countryside, said the bombardment of Homs had eased since the agreement came into force, but never completely stopped.
Two children were killed by government artillery fire in the rural town of Rastan two days ago, while another woman was killed in an air strike in the village of Kafrlaha on Tuesday, according to Mr Abou Rayan.
Outside Damascus, the Syrian Civil Defence search and rescue group said three surface-to-surface rockets struck the Hamouriya area, killing six people and wounding dozens of others, including women and children.
Video from the group showed rescuers pulling children from the rubble of a multi-storey building.