To establish potential anti-ischemic effects of testosterone and estradiol on myocardium we used isolated rat hearts in accordance with Langendorff, exposed to 40 min of ischemia and reperfusion. Rats were pretreated for 10 days, males with testosterone and females with estradiol and injuries from those hearts were compared to the hearts where both drugs were applied to the isolated hearts directly. The myocardial injuries were determined by changes in coronary flow, incidence and duration of arrhythmias and lactate dehydrogenase release rates used as markers for level of cardiac injury during reperfusion. Coronary flow in the hearts of animals pretreated with estradiol during reperfusion increased by 68.7+/-3.6% (P<0.001) and in those pretreated with testosterone by 50.1+/-2.1% (P<0.05) vs. control hearts. Lactate dehydrogenase release rates decreased in the hearts of animals pretreated with estradiol by 55.7+/-1.9% (P<0.01) vs. controls and by 58.8+/-3.0 (P<0.01) vs. directly applied estradiol. Duration of ventricular fibrillation decreased after 10 days application of drugs, from 9.42+/-0.81 min to 4.58+/-0.93 min (P<0.05) with estradiol and from 9.19+/-1.05 min to 4.65+/-0.51 min (P<0.05) with testosterone. The duration of heart arrest decreased in 10 days application of testosterone from 2.42+/-0.16 min to 20.0+/-12.26 s (P<0.01). Hearts from animals pretreated for 10 days with estradiol showed more cardioprotective effects during reperfusion than those pretreated with testosterone. Testosterone pretreatment, despite being less effective in cardioprotection than estradiol, improved coronary flow and decreased arrhythmias as effectively as estradiol.