The effect of pulsatile cardiopulmonary bypass on intramyocardial gas tensions and regional myocardial blood flow was studied in 10 mongrel dogs. Following application of a critical stenosis to the circumflex coronary artery (CIRC), animals were placed on total bypass with vented, fibrillating hearts. During three 45 minute periods of perfusion, animals alternately received pulsatile or linear flow with perfusion pressure carefully maintained at 80 mm. Hg. In myocardium supplied by the stenosed CIRC, intramyocardial oxygen tension (PO2) rose from 13 +/- 3 to 19 +/- 5 mm. Hg when a period of linear flow was followed by a period of pulsatile flow (p less than 0.025). Similarly in the CIRC-supplied area, intramyocardial carbon dioxide (PCO2) decreased from 128 +/- 12 to 99 +/- 12 mm. Hg (p less than 0.005) with conversion from linear to pulsatile flow. Myocardial blood flow (microsphere technique) to endocardial and epicardial layers of the CIRC-supplied area was significantly greater (p less than 0.05) during pulsatile than during linear perfusion. In contrast, when periods of pulsatile bypass were followed by periods of linear perfusion, myocardial PO2 fell from 25 +/- 6 to 9 +/- 3 (less than 0.02) and myocardial PCO2 rose from 82 +/- 12 to 154 +/- 12 mm. Hg (p less than 0.001). These data suggest that (1) fibrillation-induced regional ischemia distal to a critical coronary stenosis can be reduced by pulsatile perfusion during bypass and (2) the mechanism for the reduction in regional ischemia is improved myocardial blood flow.