We examined the risk factors for heterosexual transmission of HIV in a case-control study of couples in Thailand. 90 HIV-positive men and their regular sex partners were enrolled at the immune clinic, Chulalongkorn Hospital, where 92% of male index cases had HIV-1 serotype A (subtype E). Most index cases had acquired HIV through sexual intercourse. 95 couples were enrolled at 15 detoxification clinics, where 79% of them had HIV-1 serotype B (subtype B). Most men had acquired HIV through injecting drug use (IDU). The HIV seroconcordance rate was higher in the immune clinic (69%) than in the IDU clinics (48% overall, and 27% after excluding female partners who were IDUs) (p<0.01). The rate was also higher among couples in whom the male index case was infected with serotype A (subtype E) compared with serotype B (subtype B) (70% vs 52%, OR 2.1, 95% Cl 1.2-4.2). When we excluded couples in whom the female was also an IDU, the difference in concordance rates was even more pronounced (70% vs 26%, OR 6.8, 95% Cl 2.7-17.6). Viral factors or subjects' characteristrics may have contributed to the concordance rates. In a multivariate logistic regression analysis, HIV-1 serotype A (subtype E) of male partners (adjusted OR 3.1, 95% Cl 1.1-9.0) and history of IDU in female partners (adjusted OR 4.8, 95% Cl 1.4-15.9) remained independently associated with HIV seroconcordance. This study suggests that HIV-1 subtype E may be associated with higher risk of heterosexual transmission than subtype B. If so, the predominance of subtype E in Thailand may have contributed to the rapid spread of the HIV epidemic.