The US Treasury Department's spokeswoman Molly Millerwise said on Thursday that the two Syrian men had played lead roles in directing Syria's military presence in Lebanon.
The action against Interior Minister Ghazi Kanaan and the chief of Syrian Military Intelligence for Lebanon, Rustum Ghazali, means that any assets belonging to these men found in the US will be frozen.
Also, Americans are forbidden from doing business with them. The power for the Treasury Department to take the action stems from an 11 May 2004 executive order by President George Bush. Thursday's designations targeting the two Syrians were the first under that order, Millerwise said.
Reacting on Thursday, Syria slammed the assets freeze imposed on the two men as a deliberate ploy to "divert attention from Israeli aggressions" in south Lebanon.
"Syria has asked its ambassador in Washington to seek clarifications from the State Department," said an unnamed official cited by the state Sana news agency.
Syria terms the US step as a
deliberate diversionary ploy
"(Syria) is astonished by this announcement which is designed to intensify the pressure on Syria and "divert attention from Israeli aggressions" in south Lebanon.
Syria is on the US State Department's list of countries and organisations accused of supporting terrorism. Despite strained relations with the US, Syrian officials have repeatedly said they are cooperating with the US-led "war on terrorism".
The country has said all its military forces left Lebanon in April after almost three decades as the dominant political and military force there.
National elections were recently completed in Lebanon.
"We are seeking democracy to take hold in Lebanon and other places in the Middle East; yet Syria continues to support violent groups and political strife," said Treasury Secretary John Snow.
Before taking his current post as interior minister, Kanaan had served as the chief of Syrian Military Intelligence for Lebanon for 20 years, the State Department said.
He was replaced by Ghazali in late 2002.