The effects of sanguineous and asanguineous cardioplegia on the generation of myocardial acid in the hypertrophied human heart during aortic clamping and reflow were elucidated by continuous intraoperative monitoring of myocardial pH in 42 patients undergoing valve replacement, with or without coronary bypass. The patients were divided into three groups: Group I (n = 14) received intermittent crystalloid cardioplegia; group II (n = 14) received intermittent blood cardioplegia; and group III (n = 14) received continuous blood cardioplegia. The groups were matched according to six previously elucidated determinants of myocardial acidosis. Measurements were made of myocardial pH, hydrogen ion concentration ([H+]), and the difference in pH units between myocardial pH and the pH of neutrality of water at the corresponding temperature (delta pHn). Throughout aortic clamping, myocardial pH in groups I and II fell significantly by 0.46 +/- 0.08 and 0.15 +/- 0.07 units, respectively (p less than 0.001) between the groups). In contrast, myocardial pH remained statistically unchanged throughout aortic clamping in group III (p less than 0.001 compared to groups I and II). Similar relationships were observed in [H+] and delta pHn during aortic clamping. During the early reflow, myocardial acidosis was observed in all three groups and delta pHn in group III increased from -0.26 +/- 0.10 at the end of aortic clamping to -0.57 +/- 0.07 during reperfusion (p less than 0.03). Patients in groups II and III required significantly less inotropic and mechanical cardiac support than patients in group I (p = 0.017). Hence, although continuous blood cardioplegia does not completely prevent acid accumulation during reflow, it provides better metabolic protection of the hypertrophied human heart than either intermittent crystalloid or intermittent blood cardioplegia.