Human T-lymphotropic virus types I and II (HTLV-I and -II) cause myelopathy; HTLV-I, but not HTLV-II, causes adult T-cell leukemia. Whether HTLV-II is associated with other diseases is unknown. Using survival analysis, we studied medical history data from a prospective cohort of HTLV-I- and HTLV-II-infected and -uninfected blood donors, all HIV seronegative. A total of 152 HTLV-I, 387 HTLV-II, and 799 uninfected donors were enrolled and followed for a median of 4.4, 4.3, and 4.4 years, respectively. HTLV-II participants had significantly increased incidences of acute bronchitis (incidence ratio [IR] = 1.68), bladder or kidney infection (IR = 1.55), arthritis (IR = 2.66), and asthma (IR = 3.28), and a borderline increase in pneumonia (IR = 1.82, 95% confidence interval [CI] 0.98 to 3.38). HTLV-I participants had significantly increased incidences of bladder or kidney infection (IR = 1.82), and arthritis (IR = 2.84). We conclude that HTLV-II infection may inhibit immunologic responses to respiratory infections and that both HTLV-I and -II may induce inflammatory or autoimmune reactions.