Microelectrode studies in isolated cardiac tissues have shown that the depressant effect of several antiarrhythmic drugs on the maximal upstroke velocity of the cardiac action potential is rate-dependent. To determine whether this effect of antiarrhythmic drugs is seen in humans, 14 patients undergoing atrial pacing at several rates were prospectively studied before and after the infusion of procainamide (15 mg/kg). The HV interval (His-Purkinje conduction rate) and the QRS duration (intraventricular conduction rate) were measured. Before procainamide infusion, atrial pacing did not significantly prolong the maximal HV interval (from 54 +/- 15 to 58 +/- 13 ms). After procainamide infusion (mean serum level 10.0 +/- 3 micrograms/ml) atrial pacing at an average of 5 pacing rates significantly prolonged the HV interval (from 67 +/- 18 to 80 +/- 20 ms, p less than 0.001). The extent of HV prolongation with atrial pacing after procainamide infusion was independent of the HV interval at rest before procainamide. The duration of the QRS complex also tended to prolong with atrial pacing after procainamide infusion, but this prolongation was not statistically significant. Thus, procainamide produces a rate-dependent depressant effect on His-Purkinje and intraventricular conduction, confirming observations made in isolated tissue preparations.