Disease associations of human T lymphotropic virus types I and II (HTLV-I and -II) infection were studied in 154 HTLV-I-infected, 387 HTLV-II-infected, and 799 uninfected blood donors. Adjusted odds ratios (ORs) and 99% confidence intervals (CIs) were derived from logistic regression models controlling for demographics and relevant confounders. All subjects were human immunodeficiency virus type 1-seronegative. HTLV-II was significantly associated with a history of pneumonia (OR, 2.6; 99% CI, 1.2–5.3), minor fungal infection (OR, 2.9; 99% CI, 1.2–7.1), and bladder or kidney infection (OR, 1.6; 99% CI, 1.0–2.5) within the past 5 years and with a lifetime history of tuberculosis (OR, 3.9; 99% CI, 1.3–11.6) and arthritis (OR, 1.8; 99% CI, 1.2–2.9). Lymphadenopathy (⩾1 cm) was associated with both HTLV-I (OR, 6.6; 99% CI, 2.2–19.2) and HTLV-II (OR, 2.8; 99% CI, 1.1–7.1) infection, although no case of adult T cell leukemia/lymphoma was diagnosed. Urinary urgency and gait disturbance were associated with both viruses. This new finding of increased prevalence of a variety of infections in HTLV-II-positive donors suggests immunologic impairment.