The United States and its allies will respond "swiftly and appropriately" if Bashar al-Assad, the Syrian President, uses chemical weapons again, the White House cautioned on Tuesday.
The stern warning came after Russian jets struck the opposition-held city of Idlib with a barrage of air strikes hours after US President Donald Trump warned such a move would be a “grave mistake”.
The White House also said in its statement that it was closely monitoring developments in Idlib region, where the Syrian government is expected to mount an offensive that could spark a humanitarian disaster.
Dozens of strikes were reported in 24 locations around the opposition-held northwestern province of Idlib, in what appeared to be the opening salvo of the offensive.
Rebels said the strikes had targeted military positions of the Islamist group Hayat Tahrir al-Sham (HTS) and the Turkistan Islamic Party in the Jisr al-Shughour district, although at least nine civilians were reported to have been killed.
Syrian government forces have for weeks been massing around Idlib in preparation for an assault on the last-remaining opposition stronghold, with local media reporting a September 10 deadline.
Russia meanwhile has sent an armada of ships, including a Marshall Ustinov missile cruiser, to the coast of Syria in the Mediterranean.
"The government plan was to give the maximum possible chance for a reconciliation, but unfortunately there was no progress in this regards. The radicals are in control in Idlib,” a Syrian government official told the Telegraph.
“This is more than the usual stuff, it looks like preliminary bombardment before a major land operation."
President Trump had on Monday night warned the Syrian government and its Russian and Iranian allies against "recklessly" attacking Idlib.
In a tweet he warned of "a grave humanitarian mistake" in which hundreds of thousands of people could be killed.
US Marine General Joseph Dunford, chairman of the Joint Chiefs of Staff, said Russia and Syria should be looking to avoid a humanitarian catastrophe and instead recommended more narrowly tailored operations against militants there.
"If major military operations take place we can expect humanitarian catastrophe and I think we would all want to see that be avoided," Gen Dunford said.
Despite the bluster, the Trump administration is unlikely to intervene in any assault unless chemical weapons are used.
Washington has created a list of chemical weapons facilities that could be struck if Mr Trump decided to order a new round of punitive strikes.
An estimated three million people – half of them displaced from other parts of Syria – live in the province and it is expected an offensive there could become the deadliest yet in the seven-year war.
UN officials say as many as 800,000 people could be displaced and that the already high number of people in need of aid could increase dramatically.
Idlib is the only major territory the rebels still control, meaning those who do not wish to surrender to the government have nowhere left to go.
"We know that the Syrian armed forces are getting ready to solve this problem," Dmitry Peskov, President Vladimir Putin’s spokesman, said on Tuesday, calling Idlib a "pocket of terrorism."
Mr Peskov took issue with Mr Trump’s warning, saying the situation could have "dangerous, negative" consequences for the entire country.
The province is held by a complex array of rebels and jihadists, many of whom have been blacklisted as "terrorists" by world powers.
Analysts and aid workers say there is still a window of opportunity to avoid the humanitarian impact of a full-scale offensive.
The presidents of Turkey, Russia and fellow regime ally Iran are to meet at a summit in Tehran on Friday to discuss political solutions.
"It’s all building up to September 7 trilateral," tweeted Nicholas Heras, a fellow at the Centre for New American Security, who suggested Tuesday’s strikes were a warning to the opposition’s international backers.
"Russia is sending a clear message to President Trump that he can’t tell Assad to back off (…) and to (President Recep Tayyip) Erdogan to make up his mind on what are Turkey’s long term interests in Syria.