Studies were undertaken in 32 patients with hepatitis B-negative or -positive chronic active hepatitis or chronic persistent hepatitis to define the relationship between immunoregulatory activity and the HLA-BS and B12 phenotypes. Suppressor T-cell activity measured by a concanavalin A-induced suppressor system using allogeneic responder cells was dependent on which individual was selected as a source of responder cells. No differences were noted using isogeneie cells as responders. Suppressor T-cell activity measured by the effect of a noninduced suppressor cell on a mixed leukocyte culture was not different from controls. Increased prostaglandin-producing suppressor cell activity was found in patients with hepatitis B-negative ( p < 0.005) and hepatitis B-positive ( p -= 0.05) chronic active hepatitis. When results of the suppressor activities were compared among patients with chronic hepatitis dependent on the presence of HLA-B8, B12, or neither of these phenotypes, no significant differences were present. These results provide further evidence of altered immunoregulatory function in patients with chronic active hepatitis, which may reflect increased suppression by a population of prostaglandin-producing suppressor cells. The results do not, however, suggest that a gene coding for altered immune regulation is linked to HLA-_ _ -B8 or B12.