The frequencies of the hemoglobin E gene (HBB*E) and the beta-thalassemia gene(s) (HBB*T) were determined in 890 healthy adult males from three areas at the Thai-Kampuchean border in Northeastern Thailand. The population of the three study areas differs ethnically: area I is inhabited by Khmer-speaking people, area II has an ethnically mixed population (Tai-Lao, Soui and Khmer), and area III is predominantly Lao. In view of the topographic differences in malaria endemicity in the pre-eradication era, the probands from the three study areas were divided into subgroups "hills" and "plains" according to the location of their home villages. The frequencies of HBB*T were generally low, but the difference between the HBB*E frequencies in the "hills" (0.3295) and "plains" (0.2455) subgroups was highly significant. This is interpreted as environmental effect due to selection by malaria. A "hemoglobin E belt" with HBB*E frequencies between 0.3 and 0.35 extends along the Dangraek mountain chain at the border between Thailand and Kampuchea.