"The people of the UK have spoken, and we respect their decision," Obama said in a statement in his first reaction to the result of the historic referendum.
"The special relationship between the US and the UK is enduring, and the United Kingdom's membership in NATO remains a vital cornerstone of US foreign, security, and economic policy," he said.
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"The UK and the EU will remain indispensable partners of the US even as they begin negotiating their ongoing relationship to ensure continued stability, security, and prosperity for Europe, Great Britain and Northern Ireland, and the world," Obama said.
In another statement, Treasury Secretary Jack Lew said the US will work closely with both London and Brussels and international partners to ensure continued economic stability, security and prosperity in Europe and beyond.
"We continue to monitor developments in financial markets," he said.
"I have been in regular contact in recent weeks with my counterparts and financial market participants in the UK, the EU and globally and we are continuing to consult closely. The UK and other policymakers have the tools necessary to support financial stability, which is key to economic growth," Lew said.
Foreign Affairs Committee Chairman Ed Royce said the vote will not change America's special relationship with Great Britain.
"Prime Minister David Cameron's decision to step down is understandable. He is a fine leader, and I know he will do all that he can to help everyone on both sides of this debate come together and move forward. UK leadership is critical to global prosperity and security," Royce said.
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