A factorial experiment was undertaken to study the effects on systemic oxygen uptake of alteration in flow rate between 1.5 and 2.0 L.min-1.m-2, flow character between nonpulsatile or pulsatile perfusion, and acid-base management between attempted pH and alpha stat control during hypothermic cardiopulmonary bypass. Twenty-four patients undergoing elective coronary bypass were studied. After 10-minute periods of stability at moderate hypothermia (28 degrees +/- 1 degrees C), blood samples were aspirated from the arterial and venous lines. Samples were analyzed for oxygen content, saturation, and tension, pH, base excess, and lactate. Systemic oxygen uptake was significantly greater at 2.0 than 1.5 L.min-1 m-2 by 18 (7, 30) ml.min-1.m-2, whereas it was not significantly affected by change in flow character (-4[-16, 7] ml.min-1.min-2) or arterial pH (-2 [-12, 8] ml.min-1.m-2 per 0.1 pH unit). Venous oxygen tension, saturation, and content were significantly increased at the higher compared with the lower flow rate (p less than 0.05), whereas arterial oxygen tension and oxygen extraction were not. Increases in arterial oxygen content and saturation from low to high flow rates were marginally nonsignificant (F = 4.08, critical value = 4.17; F = 3.99 critical value = 4.21). Base excess was significantly affected by alteration in arterial pH but not flow rate, flow character, or stage (p less than 0.05). Lactate concentrations were unaffected by flow rate, flow character, or arterial pH, but there was a small but significant overall decrease during the course of cardiopulmonary bypass (p less than 0.05). Reasons why systemic oxygen uptake was affected by flow rate but not by flow character or arterial pH are discussed. A flow rate of 1.5 L.min-1.m-2 during cardiopulmonary bypass with moderate hypothermia results in a less than maximal systemic oxygen uptake.