We evaluated the effects of hyperthyroidism on cardiac structural changes and postischemic myocardial function, and also studied how an angiotensin-converting enzyme (ACE) inhibitor, cilazapril, can alter these changes. Hyperthyroidism was induced by daily intraperitoneal injection of thyroxine (T4) (600 microg/kg) with or without cilazapril (10 mg/kg per day, orally), and control rats were given by vehicle. After 2 weeks of treatment, T4-treated rats showed increases in blood pressure and heart weight to body weight ratio (HW:BW). Cilazapril decreased blood pressure to control values and reduced HW:BW. In the isolated working heart preparation, T4-treated rats showed a poor postischemic recovery of left ventricular pressure-rate product (14% of baseline at 30 minutes of reperfusion vs. vehicle 85%) and cardiac work (6% vs. 71%). Cilazapril recovered both values to 49% and 43%. Propranolol (500 mg/L in drinking water) decreased blood pressure to the same extent as cilazapril in hyperthyroid rats, but changed neither HW:BW nor the postischemic myocardial dysfunction. Percent recovery of cardiac work was inversely well correlated with HW:BW (R2 = 0.998, p < 0.001). Results indicate that T4-induced cardiac hypertrophy enhances postischemic cardiac dysfunction. Results also indicate renin-angiotensin system (RAS), but not sympathetic nerve activation, is involved in cardiac hypertrophy and postischemic myocardial dysfunction in hyperthyroid rats.