The demographic and geographic determinants of human T lymphotropic virus types I and II (HTLV-I and -II) are not well defined in the United States. Antibodies to HTLV-I and -II were measured in 1.7 million donors at five US blood centers during 1991-1995. Among those tested, 156 (9.1/10(5)) were HTLV-I seropositive and 384 (22.3/10(5)) were HTLV-II seropositive. In contrast to monotonously increasing age-specific HTLV-I seroprevalence, HTLV-II prevalence rose until age 40-49 years and declined thereafter, suggesting a birth cohort effect. HTLV-II infection was independently associated with an age of 40-49 years (odds ratio [OR], 12.4; 95% confidence interval [CI], 8.8-18.9), female sex (OR, 3.3; 95% CI, 2.6-4.1), high school or lower education (OR, 1.7; 95% CI, 1.3-2.1), hepatitis C seropositivity (OR, 25.0; 95% CI, 17.5-35.8), and first-time blood donation (OR, 3.6; 95% CI, 2.8-4.7). HTLV-II seroprevalence was highest at the two West Coast blood centers. These data are consistent with a 30-year-old epidemic of HTLV-II in the United States due to injection drug use and secondary sexual transmission and with an apparent West Coast focus.