The prevalence and risk factors for acquisition of human T-cell lymphotropic virus type I and II (HTLV-I and II) were investigated in a prospective study of 913 injecting drug users (IDUs) in Stockholm in 1994. Epidemiologic data were recorded, and blood samples were tested for antibodies against HTLV-I and HTLV-II; human immunodeficiency virus (HIV) types 1 and 2; and hepatitis A (HAV), B (HBV), C (HCV), and D (HDV). Positive serologic results for HTLV were confirmed by Western blot (WB) and polymerase chain reaction (PCR). Of the 905 participants with conclusive HTLV-II status, 29 (3.2%) were HTLV-II positive, and all but three were of Nordic descent. None was HTLV-I infected. One person was infected as early as 1981, before HIV had reached the IDU population in Sweden. The prevalence of HTLV-II infection was 12% among HIV-1-seropositive and 1.8% among HIV-1-seronegative participants. The overall seroprevalences were 14% for HIV-1, 0% for HIV-2, 41% for HAV, 75% for HBV, 92% for HCV, and 8% for HDV. Although amphetamine has been the main injecting drug in Sweden for several decades, heroin abuse combined with a debut of injecting drugs before 1975 was identified as the most important risk factor associated with HTLV-II infection. HAV and HIV seropositivity were also independent risk factors.