Antibody-dependent cellular cytotoxicity (ADCC) of peripheral blood lymphocytes against chicken red blood cells (ChRBC) in the presence of specific antiserum has been studied in normal subjects and in patients with acute hepatitis B and with chronic active hepatitis (CAH). ADCC was significantly reduced in patients with acute hepatitis B studied three weeks after the onset of jaundice and in patients with CAH showing clinical, biochemical and histological features of activity. On the other hand, lymphocytes from patients with CAH in histological remission or in clinical and biochemical resolution, showed a significantly increased cytotoxicity. The effect of serum factors on ADCC of normal lymphocytes was investigated using serial serum samples from five patients with acute hepatitis B and five with CAH. Our data suggest that serum factors may be responsible for the impairment of ADCC in our patients, although other mechanisms may also be implied. Sera obtained at the time when ADCC of patients' lymphocytes was reduced, significantly inhibited ADCC of normal lymphocytes when compared with sera obtained at the time when ADCC of patients' lymphocytes was normal or increased. In all cases with CAH, the disappearance or reduction of inhibiting activity correlated with histological remission. In patients with CAH the study of serum factors inhibiting ADCC of normal lymphocytes may be a useful parameter in assessing disease activity.