Clinical and immunological findings with 74 patients with chronic hepatitis C are reported. Transfusion or major surgery was noted in the case history of 69% of patients and the time elapsed from the transfusion to the diagnosis was 7.15 +/- 8.1 years in the transfused subjects. The severity of the liver disease was recorded; chronic persistent hepatitis was present in 40%, active hepatitis in 45% and cirrhosis in 15% of the patients. Cholestasis was recorded in 32%, a significant elevation of serum immunoglobulin levels was noted in 83%, an antibody to liver specific-protein (anti-LSP) occurred in 80%, cryoglobulinaemia in 44% and circulating immune complexes in 33% of the patients. Natural killer cell activity of peripheral blood mononuclear cells was significantly lower in the patients compared with the normal controls. HLA B8 and HLA DR3 antigens were found with an increased frequency (36.6% and 42.1%). Of the 74 patients, 31 were treated with recombinant interferon-alpha(2) injection sc at a dose of 3 million units (MU) three times a week (tiw) for six months. Interferon therapy normalized serum alanine aminotransferase in 45% of patients and a sustained remission was found in 26%. The treatment resulted in the clearance of HCV-RNA from the serum in 40% of patients and this correlated well with complete remission. In the responders, a decrease in CD4+ cell count and a transient decrease in CD8+ cell count as well as a moderate rise in B cell count were seen during the treatment. Mitogen-induced lymphoproliferative response and natural killer cell activity increased. Predictors of response were as follows: female sex, shorter time elapsed since transfusion, absence of HLA Al, B8, DR3 and serum anti-HBc negativity.