Autoantibodies to histone and denatured DNA have been found in 80% of patients treated with procainamide. Of these 10 to 20% will eventually develop a Systemic Lupus Erythematosus-like syndrome. Although the mechanism by which procainamide exerts its effect is unknown, in vitro studies suggest that procainamide may inhibit suppressor T cell activity. We have studied the immune function of 18 patients receiving a two hour infusion of procainamide during transvenous catheter electrophysiologic studies. There was no difference between pre and post infusion samples with respect to T and B cell mitogenesis or pokeweed mitogen-induced immunoglobulin secretion. However, in seventeen of eighteen patients, there was a marked decrease in Concanavalin A-inducible suppressor cell activity. This decrease appeared to be related to the amount of procainamide infused as high dose samples showed less suppressor activity than low dose samples. Thus the data show that procainamide, when given in vivo, leads to a rapid and dose dependent decrease in suppressor cell activity.