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White House spokesman Jay Carney's comment came as reports surfaced of armed men having taken control of two airports in the Crimea region of southern Ukraine in what the new Ukrainian leadership called an invasion.
Carney said U.S. officials are seeking clarification on the origin of the armed men.
"Intervention would be a grave mistake," he said.
He said Washington is concerned about reports that there might have been an intervention by "an outside state."
The United States has sided with the pro-Western Ukrainian leadership that took over after the departure of pro-Moscow President Viktor Yanukovich early this week.
Carney said U.S. officials have stressed in conversations with Russian officials that the territorial integrity of Ukraine must be respected. President Barack Obama spoke to Russian President Vladimir Putin a week ago.