The low mortality and perioperative infarction rates for aortocoronary bypass (ACB) make them unsuitable for evaluating the adequacy of myocardial protection. Enzymatic and functional measurements were found to be sensitive and specific indicators of myocardial injury. A prospective concurrent study of 78 patients undergoing triple ACB was conducted to evaluate the effectiveness of three popular methods of myocardial protection. Group I (32 patients) had a single dose of cold (4 degrees C) potassium cardioplegic (CPC) solution infused inducing a mean myocardial temperature (MMT) of 31 +/- 4 degrees C/min. Group II (23 patients) had multiple doses of CPC solution 8nducing a MMT of 22 +/- 2 degrees C/min. Group III (23 patients) had intermittent anoxic arrest at a MMT of 28 +/- 1 degrees C. The groups were not randomized but had comparable clinical symptoms and catheterization findings. Serial measurements of cardiac specific creatine kinase (CK-MB) revealed a peak in enzymatic activity occurring 60 minutes following ACB. The highest CK-MB was significantly (P less than 0.01) lower in group II (25 +/- 8 IU/liter) than group I (50 +/- 8 IU/liter), or group III (68 +/- 14 IU/liter). Myocardial performance was evaluated after ACB by serially measuring left ventricular stroke work index (SW) and left atrial pressure (LAP) in response to volume loading. The rise in SW was significantly (P less than 0.01) greater in group II (3.0 +/- 0.7 gm.m/sq m/mm Hg) than in group I (1.4 +/- 0.7) or group III (1.8 +/- 0.9). The highest SW attained was higher (P less than .01) in group II (43 +/- 7 gm.m/sq m) than group I (19 +/- 6) or group III (34 +/- 8) at comparable LAP values (group I: 20 +/- 5 mm Hg; group II: 18 +/- 3; group III: 18 +/- 4). Post-operative clinical evaluation failed to differentiate among the three groups. The more sensitive indices, however, demonstrated the superiority of cold, multidose cardioplegia in providing optimal myocardial protection.