An enzyme immunoassay (Ortho-HCV ELISA) for antibodies against the hepatitis C virus (HCV) was used to test 143 serum samples from 53 patients with autoimmune chronic active hepatitis (AI-CAH). Optical density (OD) values in the assay correlated closely with serum globulin (r = 0.8846, p much less than 0.0005) and IgG (r = 0.6281, p less than 0.0005) concentrations but not with immunosuppressant therapy. OD values were positive in 20 (65%) of 31 with active disease and in only 1 (5%) of 22 in remission (p less than 0.0005). The association between positive results and active disease and high serum globulin levels was confirmed by serial studies in 6 of the patients. In contrast, none of 31 patients with primary biliary cirrhosis and only 2 of 24 with non-hepatic disorders associated with high IgG concentrations were positive, and these controls showed no correlation between OD values and serum globulins or IgG. The findings suggest that serum from AI-CAH patients may contain a component that gives false-positive results in the assay.