The effects of nifedipine against ischemia- and reperfusion-induced arrhythmias were investigated using anesthetized rats with transient coronary artery occlusion. Nifedipine (5 micrograms/kg i.v.) administered 10 min prior to occlusion significantly decreased the incidence of arrhythmias occurring during 20-min coronary occlusion. The incidence and duration of reperfusion-induced ventricular fibrillation and subsequent mortality following 5-min coronary occlusion were also significantly reduced by this intervention. However, administration of nifedipine 1 min prior to reperfusion afforded no protection against reperfusion arrhythmias. To investigate whether nifedipine possesses a true antiarrhythmic action or merely extends the ischemic duration prior to reperfusion resulting in maximal rhythm disturbances, reperfusion was initiated after 3, 5, 7, 10, 20, and 30 min of ischemia. Nifedipine reduced the incidence of reperfusion-induced ventricular fibrillation after all ischemic intervals, with no change in the time of peak vulnerability to reperfusion arrhythmias. Measurements of coronary flow with 153Gadolinium microspheres indicated that flow within ischemic tissue relative to that in normal tissue was significantly increased by nifedipine. Thus, administration of nifedipine prior to occlusion affords a protective effect against ischemia- and reperfusion-induced arrhythmias, and this action is not due to extension of the ischemic duration prior to reperfusion resulting in maximal rhythm disturbances.