The plane was carrying five American soldiers and two Colombians on an anti-drug mission when it disappeared Friday.
A spokesman for the U.S. Southern Command in Miami says searchers are looking "rather vigorously" for seven survivors.
The U.S. Embassy in Bogota says State Department helicopters are participating in the rescue operation. They're focusing on Colombia's southwestern border with Ecuador, where hot, dense jungles are filled with leftist rebels.
The guerrillas often fire on low-flying Colombian military aircraft and crop-dusting planes sent to fumigate illegal drug crops. But, there's no evidence that the missing U.S. aircraft had come under attack.
The four-engine, de Havilland RC-7 took off at 1:30 a.m. Friday and was expected to return 7 1/2 hours later, said Army Capt. Chris Yates, a spokesman for the U.S. Southern Command in Miami.
The Colombians on board were air force officers, said armed forces chief of staff Gen. Rafael Hernandez.
Yates said the plane took off from a Colombian military base near Apiay, 45 miles southeast of Bogota in a mountainous region of the state of Meta.
He said there were "adverse weather conditions" including low-cloud cover Friday morning.
A spokesman at Army headquarters in Washington said RC-7's are equipped with "sophisticated electronic systems used in military command and intelligence work." A version of the aircraft is used in Korea to monitor North Korean military activities, said the spokesman, who asked that he not be identified.
Colombia, the world's No. 1 source of cocaine and a growing supplier of heroin, is the primary country of concern for U.S. anti-narcotics policy. It will receive nearly $300 million in U.S. anti-narcotics aid this year.
The U.S. Embassy recently began sharing intelligence information with Colombian military units who take part in anti-narcotics operations.
The plane's disappearance comes on the eve of a visit to Colombia by the Clinton Administration's top anti-narcotics official. National Drug Control Policy director Gen. Barry McCaffrey was scheduled to arrive Sunday for a three-day visit that includes a tour of an army base where the U.S. military is training and equipping a new, 1,500-member army counternarcotics battalion.