This retrospective study was designed to determine the relationship between human T-lymphotropic virus (HTLV) type-I/II infection and human immunodeficiency virus (HIV) infection among sexually promiscuous persons in southern India. Stored sera collected between 1986 and 1993 from 822 male and 488 female patients attending clinics for sexually transmitted diseases (STD), for the purpose of HIV serosurveillance, were used. They comprised 376 HIV-positive sera and 934 HIV-negative sera. They were screened for HTLV-I/II antibody by a particle agglutination test and repeatedly reactive sera were confirmed by an immunofluorescence test and a western blot test. Five (2.4%) of 212 HIV-seropositive men were confirmed positive for HTLV-I/II antibody, while none of the 610 HIV-seronegative men were positive; the difference in prevalence between HIV-seropositive and seronegative men was statistically significant (p < 0.001). Nine (5.5%) of 164 HIV-seropositive women and 3 (0.9%) of 324 HIV-seronegative women were positive for HLTV-I/II antibody (p < 0.005). All HIV-seropositives taken together, had a significantly higher prevalence of HTLV-I/II (3.7%; 14/376) compared with HIV seronegatives (0.3%; 3/934; p < 0.001). Thus, in southern India, HTLV infection, like HIV infection, is sexually transmitted, though less effectively.