Several electrophysiological aspects of the effects of procainamide were analyzed, using a method which allows direct study in man. The following electrophysiological parameters were determined under normal conditions in pace-maker carriers: myocardial stimulation threshold (M.S.T.), above-normal excitability phase (A.N.P.), effective refractory period (E.R.P.), pre-automatic pause (P.A.P.) and frequency of spontaneous rhythm (S.R.). After i.v. somministration of 10 mg/kg of procainamide in six subjects, and of 20 mg/kg in one, the modifications resulting from the examined parameters were analyzed. They showed that procainamide determines the constant elevation of the M.S.T., the shortening of duration of the A.N.P., lengthening of the E.R.P. and depression of the ventricular, but the superventricular automatism. Hypotheses on the electrophysiological mechanism of the observed effects are analyzed, and some clinico-electrophysiopathological correlations are traced, which help in the understanding of the anti-arrhythmic activity of procainamide.