The purpose of this study was to evaluate the acute cardioprotective effect of high-dose methylprednisolone (25 mg/kg) in the controlled in vivo model of myocardial ischemia-reperfusion injury occurring during cardiopulmonary bypass. Forty nondiabetic male patients with three-vessel disease undergoing first-time bypass surgery were enrolled for this double-blind prospective study. Patients were randomized to be given 25 mg/kg methylprednisolone (Group I) and saline (Group II) 1 h before cardiopulmonary bypass. The levels of cardiac troponin-I (cTnI) were used as a marker of myocardial tissue damage in myocardial ischemia-reperfusion injury. The cTnI levels were measured before surgery, at the second hour after cardiopulmonary bypass, at the 6th and 24th hours, and 5th day postoperatively. There was no significant difference between the two groups in respect to the duration of ischemia and reperfusion. The preoperative cTnI levels were 0.22+/-0.29 ng/ml in Group I and 0.23+/-0.28 ng/ml in Group II. cTnI levels increased to 2.40+/-1.0 ng/ml in Group I and 3.19+/-0.88 ng/ml in Group II at the 2nd hour after cardiopulmonary bypass. When the differences between T1 and T0 level that showed the amount of troponin release occurring due to ischemia-repefusion injury was calculated and then compared, there was a significant difference between Groups I and II (P=0.024). The cTnI levels measured at 6 h after CPB were 1.98+/-0.63 ng/ml in Group I and 2.75+/-1.15 ng/ml in Group II (P=0.049). cTnI levels decreased to 0.22+/-0.10 ng/ml in Group I and 0.49+/-0.25 ng/ml in Group II on the postoperative day 5 (P=0.0001). Univalent regression analysis showed that preoperative high-dose corticosteroid usage decreased the troponin release in about 12% and this effect was statistically significant (R2=0.12, P<0.05). A single dose of intravenous methylpredisolone (25 mg/kg) given 1 h before ischemia reduced myocardial ischemia-reperfusion injury. These results demonstrated that the acute cardioprotective effect of corticosteroids has much potential in the future for reducing ischemia-reperfusion injury occurring during cardiopulmonary bypass when it is inevitable.