The in vitro effect of Cyclosporin A on the regulation of immunoglobulin production was investigated in 16 patients with primary biliary cirrhosis. A significant improvement in concanavalin A induced suppression of IgG and IgM producing cells was observed after prior incubation of mononuclear cells with 300 ng/ml Cyclosporin A for 30 minutes. No effect was seen on spontaneous or pokeweed mitogen induced immunoglobulin production, nor on con A induced suppression if Cyclosporin A was added after 24 hours. Incubation of mononuclear cells with a variable dose of Cyclosporin A showed an effect only at 250-500 ng/ml. Higher and lower doses had no effect. This dose dependent effect of Cyclosporin A is likely to be related to a differential inhibitory effect on T helper and T suppressor cells and may underlie the clinical benefit being observed in current clinical trials.