There is increasing evidence that primary biliary cirrhosis is associated with an alteration of the immune system. Although the cause remains unknown, it has been suggested that the immune system of patients with primary biliary cirrhosis is involved in the pathogenesis of their disease. We have investigated the T-cell function in patients with primary biliary cirrhosis and have found defective phytohemagglutinin-induced T-cell mitogenesis. Likewise, their blastogenic response to CD3 monoclonal antibody was also depressed, although the DNA synthesis induced by stimulation with phorbol esters (12-O-tetradecanoil-phorbol-13-acetate) plus ionophore (ionomycin) was normal. These alterations could not be ascribed either to a decreased synthesis of interleukin-2 or to a defective expression of interleukin-2 receptor after cellular activation. Moreover, this defective proliferative response of T lymphocytes was observed even in the presence of saturating concentrations of exogenous interleukin-2. These results represent evidence of the deficiency in the interleukin-2-dependent pathway found in T lymphocytes from patients with primary biliary cirrhosis.