The aim of this study was to demonstrate the beneficial effects of aminophylline on protamine cardiotoxicity. Thirty-four patients were examined, 17 of whom received aminophylline 3 mg/kg before protamine administration, being the study group, while the other 17, being the control group, did not. All cardiac output and biochemical measurements were evaluated 5 min following protamine administration. The cAMP level was 43.4 +/- 3.51 pmol/ml in the study group and 18.7 +/- 2.98 in the control group (P < 0.0001) before protamine administration, while the oxygen extraction rate decreased from 49% to 44 +/- 2% in the control group, and from 51.2% to 47 +/- 3% in the study group (P < 0.03). The N-acetyl glucosaminidase value was 16.9 +/- 13.9 pmol/ml in the study group and 27.8 +/- 1.47 pmol/ml in the control group (P < 0.01), and myocardial lactate extraction was -0.20 +/- 0.03 in the control group and -0.07 +/- 0.07 in the study group (P < 0.001). The left ventricular stroke work index was 28.6 +/- 3.14 gm/m2 in the control group and 37 +/- 6.77 gm/m2 in the study group (P < 0.002). The findings of this study led us to conclude that the adverse effects of heparin neutralization using protamine can be relieved by aminophylline.