Our aims were to determine the frequency and prognostic implications of antibodies to chromatin in autoimmune hepatitis. Three hundred seventy-one serum samples from 172 patients were tested by enzyme-linked immunosorbent assay. Sixty-seven patients (39%) had antibodies to chromatin. Percent positivity was greater in men than women (58% vs 34%, P = 0.008), and seropositivity was associated with higher serum levels of gamma-globulin and immunoglobulin G. Antibodies to chromatin disappeared in 25 of 60 patients who were tested successively (42%), and they were more common in samples obtained during active than inactive disease (32% vs 19%, P = 0.01). Relapse after drug withdrawal occurred more often in seropositive patients (91% vs 66%, P = 0.002). We conclude that antibodies to chromatin occur commonly in autoimmune hepatitis, and they are associated with disease activity. Percent positivity is greater in men than women, and seropositivity identifies individuals who commonly relapse after drug withdrawal.