Former US presidential candidate John McCain, a Republican Senator, said: "I think the repercussions are incalculably huge...If it is the result of either separatist or Russian actions mistakenly believing this is a Ukrainian warplane, I think there's going to be hell to pay, and there should be."
The extraordinary pictures of smoke billowing from Flight MH17 are being watched closely in London and Washington, but there are few clues about how the West can respond.
David Cameron and Barack Obama have stepped up the rhetoric aimed at Russia, but it has fallen largely on deaf ears. Now nine Britons and 27 Australians, according to Dutch authorities, and fears of up to 23 Americans have lost their lives to the conflict, it will be harder to stay on the sidelines.
If it emerges that pro-Russian separatists brought down the Malaysia Airlines flight, it will further increase Vladmir Putin's status as a pariah on the world stage - something he appears to revel in.
Since Russian troops seized Crimea in March, Britain and America have been strong on condemnation but unable to back it up with significant action.
Pro-Russian separatists have shot down military aircraft in the past, but downing a passenger aircraft with 295 people would be a new low. So far at least no-one is taking responsibility.
Richard Miniter, best-selling author and national security expert, forecasts that the tragedy will increase international suspicion towards Russia.
He said: "I think this is bad news for Russia, despite attempts to put blame on the Ukrainian military. It wouldn't be in Ukraine's interest to bring down a civilian aircraft in their airspace."
He added that the Ukrainian forces are unlikely to have mistakenly brought down a civilian flight at 30,000ft as military aircraft either fly much lower in order to strafe ground units or much higher to bomb targets.
- Daily Mail