In 20 patients receiving cold crystalloid cardioplegia (n = 10) or cold blood cardioplegia (n = 10) during elective coronary artery bypass grafting, the atrial myocardium was tested for glutathione-related antioxidant defenses and lipid peroxidation. In both groups, ischemia and reperfusion induced a significant increase in lipid peroxidation values (p < 0.05) that was associated with a depression of nonprotein thiol compound levels (p < 0.05). Compared with the cold crystalloid cardioplegia-treated patients, the cold blood cardioplegia-treated patients showed a lower lipid peroxidation (p < 0.05) and higher values of nonprotein thiol compounds (p < 0.05). Moreover, a significant ischemia and reperfusion-dependent activation of glutathione transferase was observed only in the cold crystalloid cardioplegia-treated patients. Selenium-dependent glutathione peroxidase and glutathione reductase activities did not change after release of the aortic cross-clamp and did not differ between the two groups. The highest postoperative plasma level of the myocardial-specific isoenzyme of creatine kinase was significantly more elevated in the cold crystalloid cardioplegia patients. Overall, these tissue biochemical features indicate a lower oxidant burden in the myocardium of cold blood cardioplegia-treated patients, a finding suggesting superior protection for the ischemic and reperfused human myocardium also through antioxidant-type mechanisms, apparently medicated by the antioxidant capacity of erythrocytes and specific plasma molecules.