A community-based cohort study was conducted to clarify the risk of human T-cell leukemia virus type I (HTLV-I) infection for cause-specific deaths. A total of 1,997 individuals (751 men and 1,246 women) aged 30 or older in A-Island, Nagasaki Prefecture, Japan who had voluntarily attended annual mass health examinations, including serum HTLV-I antibody test, were followed up for a mean period of 5.3 years. In a Cox proportional hazards analysis adjusted for age at baseline, the HTLV-I seropositivity was found to be associated with mortality from all causes in men (hazard ratio (HR) 1.89; 95% confidence interval (CI) 1.01-3.54) and women (HR 1.94; 95% CI 1.16-3.22). When the effects of 2 deaths (1 man and 1 woman) from adult T-cell leukemia/lymphoma (ATL) were excluded, the mortality risk decreased slightly but was still significantly or marginally significantly greater than 1 in both men (HR 1.77; 95% CI 0.93-3.37) and women (HR 1.87; 95% CI 1.12-3.12). Further analysis of cause-specific deaths revealed a significant increase in the risk for non-neoplastic diseases but not for neoplasms excluding ATL. These findings suggest that long-term HTLV-I infection represents a health hazard greater than just that for the development of ATL. It was difficult, however, to draw a conclusion regarding the association between HTLV-I infection and cancer risk, because the number of cancer deaths was small and the incidence of cancer was not investigated.