Reperfusion after a brief period of cardiac ischemia can lead to potentially lethal arrhythmias. Importantly, there are sex differences in cardiac physiology and in the types and severity of cardiac arrhythmias. Therefore, we tested the hypothesis that gonadal hormones influence the susceptibility to reperfusion-induced sustained ventricular tachycardia as well as the response to beta-adrenergic receptor blockade. Male and female intact and gonadectomized rats were instrumented to record arterial pressure, temperature, ECG, and cardiac output. In addition, a snare was placed around the left main coronary artery. The susceptibility to sustained ventricular tachycardia produced by three minutes of occlusion and reperfusion of the left main coronary artery was determined in conscious rats by pulling on the snare. Reperfusion culminated in sustained ventricular tachycardia in 77% of female rats (susceptible 10/13) and 56% of male rats [susceptible 9/16 (p>0.05 male vs female)]. Beta-adrenergic receptor blockade prevented sustained ventricular tachycardia in females only [susceptible female 1/9, 11% vs susceptible male 6/9, 67% (p<0.05)]. Ovariectomy did not significantly reduce the susceptibility to reperfusion arrhythmias (susceptible 5/9, 56%). In sharp contrast, orchidectomy significantly increased the susceptibility to reperfusion arrhythmias (susceptible 9/9, 100%). Finally, beta-adrenergic receptor blockade prevented sustained ventricular tachycardia in ovariectomized females (susceptible 0/4, 0%) and orchidectomized males (susceptible 0/7, 0%), but the protective effect of beta-blockade was due to a reduction in heart rate in males only. Thus gonadal hormones influence the susceptibility to reperfusion-induced arrhythmias as well as the effects and mechanisms of beta adrenergic receptor blockade.