Antibody response to the E2/NS1 protein of the hepatitis C virus (HCV) was studied in 26 patients with post-transfusion acute hepatitis C. Second-generation HCV (HCV-2) antibody, E2/NS1 antibody and HCV-RNA were measured in serial serum samples taken within 1 month and 3, 6 and 12 months after the onset of acute hepatitis C. The HCV genotype was also tested to study its clinical significance. Of 26 patients, eight showed normalization of alanine aminotransferase (ALT) and clearance of HCV-RNA (resolved group). In the remaining 18 patients, HCV viraemia and ALT abnormality (except one patient) continued for more than 3 years (unresolved group). Both HCV-2 and E2/NS1 antibodies were positive at least once in all patients. The prevalence of E2/NS1 antibody was significantly (P < 0.05) higher in the resolved group (88%) than in the unresolved group (39%) in the period within 1 month of onset; the prevalence was similar between the two groups thereafter. The prevalence of HCV-2 antibody did not differ between the two groups at any point. The HCV genotype was not related to the chronicity of acute hepatitis C. In conclusion, the E2/NS1 antibody appeared in all patients with acute hepatitis C and was associated with the clearance of HCV.