The relation between high current atrial stimulation and antiarrhythmic drugs was not clear. We evaluated the effects of procainamide and dl-sotalol on the electrophysiological changes induced by high current stimulation. Effects of high current atrial stimulation on effective refractory period, dispersion of refractoriness, conduction velocity, and wavelength of the earliest atrial premature beat were evaluated at baseline and after infusion of procainamide (10 patients) and dl-sotalol (10 patients). High current atrial stimulation shortened effective refractory period locally (-12% +/- 4.0%, -7.0% +/- 3.0%, -5.1 +/- 3.3%, and -3.0 +/- 2.0%, at 0, 7, 14, and 21 mm from the S1 stimulation site, respectively; P < 0.001); increased the dispersion of refractoriness (from 17.8 +/- 8.5 to 27.4 +/- 12.5 ms, P < 0.001); decreased conduction velocity of the earliest premature beat (from 0.58 +/- 0.10 to 0.52 +/- 0.09 ms, P = 0.01); and decreased wavelength of the earliest atrial premature beat (from 10.9 +/- 2.4 to 8.8 +/- 2.1 cm, P < 0.001). These effects of high current stimulation persisted after procainamide infusion. However, after dl-sotalol infusion, high current atrial stimuli did not change the dispersion of refractoriness (23.1 +/- 10 ms vs 26.4 +/- 10.4 ms; P > 0.05, twice diastolic threshold vs 10 mA); conduction velocity of the earliest premature beat (0.54 +/- 0.06 ms vs 0.50 +/- 0.06 ms, P > 0.05); or wavelength of the earliest premature atrial beat (11.5 +/- 1.6 m/s vs 10.1 +/- 1.7 cm; P > 0.05). Although high current atrial stimulation shortened effective refractory period locally, increased dispersion of refractoriness, and decreased the wavelength of the earliest premature atrial impulse, these effects were abolished by dl-sotalol but not procainamide.