This study of anesthetized, open-chest dogs compares the effects of primary increases in left ventricular preload and afterload upon global and regional myocardial function and metabolism in the presence of a left anterior descending coronary artery stenosis (LAD). When LAD flow was reduced to 40-50% of control, regional systolic shortening declined by 20 to 25% and regional lactate extraction changed to production. In seven control dogs the mechanical abnormalities persisted during the 30 min of observation, but lactate production was reduced spontaneously. In ten dogs, increases in left ventricular end-diastolic pressure (LVEDP) during dextran infusion were associated with increases in cardiac output and regional systolic shortening; however, regional lactate production also increased (P less than 0.05) despite an augmentation in LAD flow. In seven dogs mean arterial pressure increased by an average of 32 mm Hg during angiotensin infusion (0.2 to 0.4 mug/kg/min); LVEDP did not change but cardiac output decreased significantly. LAD artery flow improved markedly and lactate production shifted to extraction (P less than 0.05) while systolic shortening remained unchanged. When angiotensin was discontinued, lactate extraction worsened again. Thus, in the presence of a severe coronary stenosis, a primary increase in preload improves cardiac output but at the expense of aggravated ischemia. In contrast, a primary increase in afterload reduces cardiac output but may improve perfusion and lactate uptake of the ischemic myocardium.