The speaker of the US House of Representatives, Nancy Pelosi, is to visit Syria early next week despite objections by the White House.
It will be Ms Pelosi's second trip to the Middle East this year
Ms Pelosi will lead a delegation from US Congress for talks with officials.
She will be the most senior member of Congress to visit Syria since relations between the two countries soured.
Washington withdrew its ambassador to Damascus two years ago after the murder of former Lebanese PM Rafik Hariri, in which Syria denies any involvement.
The BBC's Vanessa Heaney in Washington says Nancy Pelosi's second trip to the Middle East this year shows she has no intention of letting President Bush dominate foreign policy.
Syria's embassy in Washington described the trip as "momentous" and expressed hopes it may change strained relations with the United States, AFP news agency reported.
President Bush has consistently refused to engage with Syria. On Friday, the White House denounced Ms Pelosi's plan, calling it "a really bad idea".
Spokeswoman Dana Perino said the House speaker "should take a step back and think about the message that it sends".
"This is a country that is a state sponsor of terror, one that is trying to disrupt the Siniora government in Lebanon and one that is allowing foreign fighters to flow into Iraq from its borders."
Syria has denied it allows insurgents to cross from its territory into Iraq, saying Iraq and the US have not done enough to police the border.
There have been recent calls in the US to engage, rather than isolate Syria.
Earlier this year, a bipartisan US commission recommended the Bush administration launch diplomatic initiatives with both Syria and Iran - something President Bush has refused to do.
Ms Pelosi is currently in Israel where she is expected to meet Prime Minister Ehud Olmert, before travelling to the West Bank to meet Palestinian President Mahmoud Abbas.
In late January, she led a delegation of House members to Iraq, Afghanistan, Israel and other neighbouring countries.