Secretary of State John Kerry warned Syrian President Bashar Al-Assad on Tuesday there would be "repercussions" if his regime flouts a new ceasefire being negotiated with Moscow for the battered city of Aleppo.
A February 27 truce between the Syrian regime and non-jihadist rebels raised hopes for efforts to resolve the five-year conflict.
But it has all but collapsed amid renewed fighting, the worst of it in Aleppo, where a surge in violence has claimed more than 270 lives since April 22.
"If Assad does not adhere to this, there will clearly be repercussions and one of them may be the total destruction of the ceasefire and they go back to war," Kerry told reporters.
"I don't think that Russia wants that. I don't think that Assad is going to benefit from that," he added, after returning from a trip to Geneva where he tried Monday to save the truce.
"There may be even other repercussions that are being discussed but that is for the future to determine."
Kerry also renewed pressure for Assad to step down, with some dire warning about his future.
The truce "will not hold unless there is a bona fide effort to put in place a transition," he said, noting an August 1 target date for a change of power.
"So either something happens in these next few months, or they are asking for a very different track."
Russia said earlier on Tuesday it hoped a new ceasefire could be announced within hours for Aleppo, while the UN Security Council is due to meet Wednesday to discuss the crisis in the city.
"Everybody at the table has said you can't end this as long as Assad continues, because Assad cannot reunite the country. It's that simple," Kerry said.
"Having gassed his people, barrel-bombed his people, dropped bombs on hospitals, driven 12 million people out of their homes, tortured people, starved people -- what kind of legitimacy should somebody who's committed these kinds of atrocities suddenly claim to run the country?
"It's pretty hard for anybody to understand how you make peace out of that record of chaos and depravity."
Washington and Moscow are now working together to include Aleppo in a freeze in fighting aimed at bolstering the broader truce brokered by both world powers.
"The cessation of hostilities was put in place precisely to give the people on the ground who are innocently caught between these warring factions some breather, some ability to be able to be safe and work this out at the negotiating table," Kerry said in condemning the latest violence.
"That is why we are working urgently right now to reaffirm the cessation of hostilities nationwide."
AFP contributed to this report.