A cross-sectional seroprevalence study of human immunodeficiency virus type 1 (HIV-1) and human T-cell lymphotropic virus type I (HTLV-I) was undertaken among 494 attendees in two Santo Domingo sexually transmitted disease clinics in 1989. All participants were evaluated for Neisseria gonorrhoeae, Chlamydia trachomatis, syphilis, and genital ulcers. Of the 494 participants, 15 (3.0%) were positive for HIV-1 and 14 (2.8%) were positive for HTLV-I. Twelve of 371 (3.2%) men were HIV-1 seropositive: 0 of 68 homosexual/bisexual and 12 (4.0%) of 302 heterosexual men (one seronegative male could not be classified). Three (2.4%) of 123 women were HIV-1 seropositive. One (1.5%) homosexual/bisexual man, five (1.7%) heterosexual men, and eight (6.5%) women were HTLV-I seropositive. Among heterosexual men, HIV-1 was associated with multiple lifetime sex partners (O.R. = 5.9; 95% C.I. = 1.4, 23; p = 0.007). HIV-1 was associated with genital ulcer disease among women (p = 0.004). Among women, HTLV-I was associated with professional sex work (O.R. = 18; 95% C.I. = 2.1, > 100; p = 0.001). These findings suggest the need for control of sexually transmitted diseases and targeted educational programs for prevention of HIV-1 and HTLV-I among individuals with high-risk behaviors in the Dominican Republic.