Intravenous drug users (IVDUs) in Seattle (n = 213) were studied to identify the prevalence and predominant types of and risk factors for human T cell lymphotropic virus (HTLV) infection. Detailed questionnaires, serologic screening, and polymerase chain reaction analysis (for a subset) were used. Evidence of HTLV infection was found in 16.5%, of which 89% were HTLV-II. HTLV infection was significantly associated with nonwhite race, older age, more years of intravenous drug use, prior use of heroin, history of gonorrhea, history of any sexually transmitted disease, hepatitis B virus infection, and antibody to herpes simplex virus type 2 (HSV-2). By stepwise logistic regression analysis, associations persisted with race, age, hepatitis B markers, and HSV-2. Thus, the strong association of HTLV with hepatitis B, a marker for injection behavior, and the independent association with HSV-2 infection, a sexually transmitted pathogen, suggest similarities in the epidemiology of HTLV and human immunodeficiency virus infections in IVnUs. © 1994 The University of Chicago.