The effect of aprindine, verapamil and nifedipine on electrical stimulation threshold (EST) and ventricular fibrillation threshold (VFT) was studied in isolated rabbit hearts. Aprindine steeply raised EST and VFT in a dose-dependent manner. With the highest concentration of aprindine tested (0.56 mumol/l), protection against electrically-induced ventricular fibrillation was achieved in 4 out of 6 hearts after 60 min exposure to the drug. Perfusion with verapamil (0.1 and 0.2 mumol/l) and nifedipine (0.14 and 0.21 mumol/l) produced significant rise in both thresholds. When the hearts were perfused with higher concentration (0.3 mumol/l verapamil, 0.28 mumol/l nifedipine), EST and VFT did not continue to be increased in a dose-dependent manner but actually dropped below the control value in most hearts. These results suggest that the effect of aprindine on EST and VFT is different from that of verapamil and nifedipine and further indicate a limited effectiveness of these two slow channel blockers against ventricular fibrillation.