Suppressor T-cell activity and allogeneic T-cell response to concanavalin A (ConA) were investigated in 46 patients chronically infected with hepatitis B virus (HBV). Thirty-eight patients had chronic active hepatitis, seven of whom were superinfected with Delta virus, and eight were healthy chronic HBV carriers. T-cell suppressor activity was in the normal range in healthy carriers and in patients negative for serum HBV-DNA, independent of the e antigen status. In contrast, the group of patients positive for HBV-DNA exhibited a significant reduction in suppressor activity. Longitudinal studies in patients who cleared serum HBV-DNA demonstrated that suppressor T-cell activity became normal thereafter. These results suggest a relationship between suppressor T-cell function and the stage of viral replication in individuals with chronic HBV infection.