The effect of aprotinin, a protease inhibitor, on myocardial interleukin-8 (IL-8) production after ischemia-reperfusion injury was investigated. Twenty patients who had elective coronary artery bypass grafting were included in this study. Patients were randomly divided into two groups (n = 10 in each). Group A patients received high dose aprotinin (20,000 IU/kg as pretreatment followed by 7500 IU/kg for 6 h) and Group B patients received normal saline as a control. Serum IL-8 levels after the termination of cardiopulmonary bypass (CPB) showed a significant improvement in aprotinin treated group compared to control group (70 +/- 42.6 vs 360.71 +/- 87.9 ng/ml) (P < 0.005). Levels were also significantly higher at post-operative 24th hour in patients who did not received aprotinin (340.16 +/- 92.10 vs 96.13 +/- 34.33 ng/ml). However at post-operative 48th hour levels were again higher in control (untreated) group, but the difference was not statistically significant (78.8 +/- 34.4 vs 42.8 +/- 9.29 ng/ml). Aprotinin prevented the IL-8 release from myocytes in ischemia-reperfusion injury. The mechanism is highly dependent on anti-protease activity of aprotinin.