Syrian government forces have reportedly fired scud missiles at opposition fighters for the first time in the two-year civil war.
Unnamed US officials said the regime had fired the weapons from the capital Damascus into northern Syria.
A Nato official also said that a number of short-range ballistic missiles had been launched inside Syria this week.
It was not immediately clear why President Bashar al Assad's forces would deploy scud missiles, which can have a range of up to a few hundred kilometres and are best-known internationally from the 1991 Gulf War when the then Iraqi leader Saddam Hussein fired them at Israel.
The White House said if true, it was a sign of Mr Assad's "desperation" amid a growing army of rebel fighters, "more unified and organised" than ever before.
News of the development comes on the same day as a car bomb and two other explosives ripped through the main entrance of the Syrian interior ministry in Damascus, reportedly killing and injuring dozens of people.
White House spokesman Jay Carney, said he could not confirm the report of scud missiles being used, but told reporters: "If true, this would be the latest desperate act from a regime that has shown utter disregard for innocent life.
"The idea that the Syrian regime would launch missiles within its borders at its own people is stunning, desperate and a completely disproportionate military escalation."
Sky's US correspondent Dominic Waghorn said the "significance" of the potential development was "because of what you can put into scud missiles".
"You can put chemical, biological warheads into a scud missile, and fire at some distance to cause enormous damage, without damage to your own forces," he said.
Last week, US President Barack Obama warned Mr Assad of the "consequences" of using chemical weapons against his own people after security officials said they had detected activity at chemical weapons depots.
Mr Obama has made clear such action would cross "a red line" for the United States that would prompt action.
There were reports that up to seven people had been killed and 50 injured in Wednesday's attack on the Syrian interior ministry in the southwest district of Kafar Souseh - a battleground for rebels and forces loyal to Mr Assad.
The Syrian Observatory for Human Rights, an opposition group based in the UK, said there were 25 casualties.
Syrian state TV, which reported the blasts, said interior minister Mohammad al Shaar and other top ranking officials escaped unharmed.
The pro-government TV station Al Ikhbariya aired footage of concrete rubble, blood on the floor and two-metre-wide hole in the road.
The adjacent building housing the Egyptian embassy was also hit, Egypt's official MENA news agency reported.
The conflict, which has claimed the lives of least 40,000 people since March 2011, has intensified and has been centred in and around the capital in recent months - and it is not the first time government and national security buildings have been targeted.
On July 18, the president's brother-in-law Assef Shawket, defence chief Daoud Rajha, and General Hassan Turkmani, a former defence minister and senior military official, were all killed in a bomb attack at a meeting of senior security and government figures in Damascus.
And more recently, more than 50 people were killed after two car bombs went off in Jaramana on November 28.
Meanwhile, the US has joined several other western and Arab nations in formally recognising Syria's opposition coalition as the legitimate representative of the nation's people.
France, which with the UK has already formally recognised the Syrian National Coalition as the government-in-waiting, said more than 100 nations had now followed suit.
The apparent breakthrough came after British Foreign Secretary William Hague told the Friends of Syria meeting in Morocco that he was "deeply disappointed by the failure of the international community" to throw its weight behind it.
"We do not know how long the conflict in Syria will last," he said.
"Helping the National Coalition to win the confidence of the Syrian people, planning for a peaceful future for the country and protecting the victims of the conflict on whom that future will rest, is surely the right way to seek to end the conflict and stop the appalling loss of life," he added.