The cause of the crash of the DC-3 aircraft was not immediately known.
Civil defense chief Angel Rangel said 21 passengers and three crew were killed when the aging plane, owned by the small regional airline Rutaca, crashed in the outskirts of Ciudad Bolivar at 6 p.m. local time (5 p.m. EST).
The Globovision television channel said the dead comprised five Dutch passengers, four Italians, two Hungarians, six U.S. citizens, one Austrian and six Venezuelans, including the four-man crew.
Globovision released a list of passengers' names, but airline and airport officials could not be reached independently for confirmation.
The tourists were flying from the popular holiday destination of Canaima to the Caribbean island of Margarita.
Rangel said the pilot had just taken off after refueling in Ciudad Bolivar, about 300 miles southeast of Caracas, when he reported difficulties.
The plane was attempting to return to the airport when it burst into flames in mid-air and plunged into a slum. Two children on the ground were being treated for severe burns, Rangel said.
Luis Alberto Guzman, director of the newspaper El Expreso Bolivar, said the 22-year-old mother of the children, aged 6 months and 2 years, also was injured.
Television showed rescue workers carrying charred bodies from the wreckage, which was still in flames more than four hours after the crash.
Rutaca is a cargo and passenger carrier based in Ciudad Bolivar, Globovision reported.
Rutaca flies to Trinidad, Guyana and Venezuelan tourist destinations such as Canaima, gateway to Venezuela's famed Gran Sabana territory, an area of lush tropical foliage, soaring mesas and Angel Falls, the world's highest waterfall.
The DC-3 is a U.S.-built, twin-propeller aircraft built in the 1950s.
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