Russian officials have accused the United States of siding with "terrorists" in Syria, in a sign of escalating tensions between Moscow and Washington amid the battle for Aleppo.
US State Department spokesman John Kirby's warning that the collapse of US-Russian cooperation in Syria could lead to a rise in extremism and potential attacks against Russia drew Moscow's anger.
The Russian Foreign and Defence Ministries both cast it as US encouragement of terror attacks on Russia.
"We can't assess those statements as anything else but a call, a directive for action," Foreign Ministry spokeswoman Maria Zakharova said at a briefing.
Defence Ministry spokeswoman Maj Gen. Igor Konashenkov said Mr Kirby's statement amounted to "the most frank confession by the US side so far that the whole 'opposition' ostensibly fighting a 'civil war' in Syria is a US-controlled international terrorist alliance".
"What makes Kirby's statement particularly shocking is that the scale of direct US influence on terrorists' activity is global and reaches as far as Russia," he added.
The remarks by Russian officials have shown a degree of mistrust and strain between Moscow and Washington after the collapse of the US-Russia-brokered truce and the Syrian army onslaught on Aleppo backed by Russian warplanes.
The growing friction makes it increasingly unlikely that the ceasefire could be revived.
US Secretary of State John Kerry threatened on Wednesday to cut all cooperation with Moscow on Syria unless an onslaught on Aleppo ends.
This 7-year-old girl is live-tweeting what it's like living in Aleppo. pic.twitter.com/li3Iq49os0— AJ+ (@ajplus) September 29, 2016
Mr Kirby, asked what the consequences would be for Russia if cooperation with the US in Syria collapsed, said: "That extremists and extremists groups will continue to exploit the vacuums that are there ... which will include, no question, attacks against Russian interests, perhaps even Russian cities, and Russia will continue to send troops home in body bags."
Mr Konashenkov interpreted Mr Kirby's statement as a direct threat to the Russian military in Syria.
He said that Russia remains open for dialogue with Washington on Syria, but added that the US needs to "exclude even a hint at threatening our military and Russian citizens".
President Vladimir Putin's spokesman Dmitry Peskov said that Moscow still wants to cooperate with Washington on the Syrian crisis, but blamed the US for a failure to deliver on its pledge under the September 9 agreement to encourage moderate opposition to sever ties with al Qaida's branch in Syria.
"Our colleagues from Washington have tried to cover up their inability to fulfil their own obligations with verbal attacks on Russia," he said.