Hypergammaglobulinemia, mainly due to increased serum immunoglobulin M concentrations, is a common and distinctive feature of primary biliary cirrhosis. T-B cell cooperation plays a pivotal role in the regulation of immunoglobulin secretion. In this paper, the production of regulatory B lymphokines by T cells, as well as the functional response of B lymphocytes to these molecules, was investigated in patients with primary biliary cirrhosis. T cells from patients with primary biliary cirrhosis have an enhanced ability to produce lymphokines that regulate the proliferation of B cells and their differentiation to immunoglobulins G- and M-secreting cells. In contrast, the cellular production of lymphokines involved in the induction of immunoglobulin A-secreting cells was normal. Simultaneously, the proliferation and differentiation of purified B cells in response to stimulation with surface immunoglobulin ligands and lymphokines were normal. These results suggest that the elevated serum levels of immunoglobulins M and G found in patients with primary biliary cirrhosis could be ascribed to an enhanced lymphokine-mediated T-B cooperation.