Antibody-dependent cell-mediated cytotoxicity was studied in patients with chronic active hepatitis (CAH) and normal controls (N) using a non-immune allogeneic lymphocytes and cultured rat parenchymal cells (Coon cells). Normal non sheep erythrocyte rosette forming cells (non E-RFC) alone showed a mild cytotoxicity to Coon cells in the absence of human sera (21.5 +/- 1.5) and in the presence of N sera (26.0) +/- 1.5) and in the presence of N sera (29.0) +/- 5.1), however, preincubation of Coon cells with CAH sera significantly augmented the cytotoxic activity of normal non E-RFC (49.4 +/- 8.7). This was blocked by aggregated IgG, anti-IgG and anti-IgG/Fc. CAH sera absorbed with Coon cells or rat hepatocyte-surface membranes failed to induce significant target cell lysis. In the absence of normal non E-RFC, N and CAH sera alone did not provoke cytotoxicity to Coon cells. Using membrane immunofluorescence method membrane-fixed IgG on target Coon cells was demonstrated in 7 of 10 sera from CAH. It seems likely that the IgG.antibody-dependent cell-mediated cytotoxicity may play a role in pathogenesis of CAH.