Suppressor T cell activity was studied serially in 11 patients with HBsAg-negative chronic active hepatitis when the disease was clinically and histologically inactive and during relapse using a short-lived suppressor cell assay. With a concentration of concanavalin A which gave a suboptimal proliferative response in normal subjects, the expected increase in thymidine incorporation was seen when the addition of the mitogen was delayed for 24 hr after the start of the lymphocyte culture period, a finding consistent with the disappearance of functional suppressor cells during the initial incubation. This effect was seen both in normal subjects and in patients with inactive disease, but was not observed at times of relapse. Further studies revealed a marked increase in lymphocyte sensitivity to concanavalin A at these times, a finding which might explain the apparent decrease in suppressor cell activity. When lower concentrations of mitogen were used in the assay, however, a significant reduction in suppressor cell activity was observed in the patients with chronic active hepatitis which was almost equal in magnitude in both the active and inactive groups, suggesting the presence of a true suppressor cell defect in this disease.