A follow-up study was performed to analyze the effects of hepatitis C virus (HCV) infection on morbidity and mortality in the adult population from a village in Japan found to have endemic levels of both HCV and human T lymphotropic virus type I (HTLV-I). By use of the Cox proportional hazards model, rate ratios (RRs) and 95% confidence intervals (CIs) were estimated. Strong, significant effects of seropositivity for antibodies to HCV on self-reported incident liver disease (RR, 3.5; 95% CI, 1.9-6.4) and on death due to liver cancer (RR, 8.2; 95% CI, 1.6-41.4) were observed. Dual infection with HCV and HTLV-I seemed to have a synergistic effect on incident liver disease (RR, 5.9) as well as on death from liver cancer (RR, 21.9). HCV infection also was positively, although not significantly, associated with reported incident diabetes. Our findings suggest that coinfection with HTLV-I may affect the course of HCV-associated disease.