The MCS was established in 1984 to evaluate the natural history of HTLV-I in two endemic communities in southwestern Japan; the prevalence of infection is currently 27% among the nearly 2000 participants. It was recently discovered that one of these communities also has a prevalence of HCV of about 26%. The plan is to extend and expand the preliminary studies on the natural history of HCV, to consolidate the work on the natural history of HTLV-I, and to evaluate the effect of co-infection of these two newly identified viruses. Specifically, the application proposes: to describe the pattern and distribution of seromarkers of HCV infection; to examine the stability of markers within the host, over time; to develop an operational definition of HCV infection; to evaluate the relevance of various HCV seromarkers with respect to liver function over time and in relation to reported liver disease; to investigate the effect of HCV infection on overall and cause-specific morbidity and mortality; to evaluate whether there is evidence that HCV infection is immunosuppressive; to describe the viral marker profiles in subjects co-infected with both HCV and HTLV-I; to identify the HTLV-I viral markers and demographic risk factors predictive of proviral clonality among carriers; to evaluate the interaction of HTLV-I infection and Helicobacter pylori in the risk of peptic ulcer and of gastric cancer; to describe the evolution of HTLV-I parameters in seroconvertors and to identify additional viral correlates of transmission from infected spouses; to evaluate the levels of various soluble T-cell surface markers as an index of viral status.