Primary biliary (PBC) has many features, suggesting immunopathogenic mechanisms involved in its etiology. However, none of the therapeutic modalities that are beneficial in many autoimmune diseases have been demonstrated to halt histologic progression of the disease or to induce a complete clinical, biochemical, and histologic remission on this disease. To investigate whether corticosteroids improve the abnormal immunoregulatory functions in PBC, the in vitro effect of corticosteroid on the activity of suppressor T cells and interleukin 2, an inducer of immunoregulatory cells, was evaluated in eight patients with PBC. Defective suppressor T cell activity was found in PBC; however, no clear improvement of T cell activity was observed after in vitro treatment of lymphocytes with corticosteroid. In PBC, interleukin 2 activity was normal, and the same decrease of activity as occurring in healthy controls was observed after corticosteroid treatment. These results suggest that a defect in the responsiveness of suppressor T cell activity to corticosteroid may play, at least in part, a role in the pathogenesis of corticosteroid ineffectiveness in PBC.