Hepatitis C virus antibodies are found in the serum of most patients with chronic hepatitis C. However, the significance of the humoral response is still uncertain. In this study, in vitro IgG and IgM anti-hepatitis C virus secretion by peripheral blood mononuclear cells of patients with chronic hepatitis C was analyzed. Peripheral-blood mononuclear cells from 21 of 36 patients (58.3%) secreted IgG anti-hepatitis C virus in vitro, as demonstrated with anti-hepatitis C virus-specific enzyme immunoassays and recombinant immunoblot assays. Ten of the 36 patients (27.8%) showed both IgG and IgM anti-hepatitis C virus core in vitro. In 9 of these 10 patients, IgM anti-hepatitis C virus was also detected in serum. Patients with in vitro IgM or IgG anti-hepatitis C virus secretion had higher ALT levels in serum than did patients without such secretion in vitro (99.5 +/- 22.1 and 85.6 +/- 34.4 vs. 38.1 +/- 37.4 U/L; p < 0.0001, p < 0.001). Furthermore, with a histology activity score it was demonstrated that patients with in vitro IgM or IgG HCV antibodies (or both) had more severe chronic active hepatitis than did patients without in vitro hepatitis C virus antibody secretion (p < 0.01). To analyze the therapy outcome, we included in this study 18 patients who had received interferon-alpha previously. Seven of eight in vitro hepatitis C virus antibody-positive patients were nonresponders, whereas the in vitro hepatitis C virus antibody-negative patients were mostly complete therapy responders (8 of 10).(ABSTRACT TRUNCATED AT 250 WORDS)