The response of global cardiovascular and regional myocardial function (as seen with sonomicrometry) to continuous, progressive hemodilution (Dextran 70) was compared in dogs with proximal circumflex coronary artery stenosis and dogs with proximal circumflex coronary artery and proximal left anterior descending artery stenoses. Hemodilution-induced failure, defined as greater than 50% loss in function or death of the animal, was determined for systolic shortening in the circumflex coronary artery and left anterior descending artery territories, mean arterial pressure, and maximum left ventricular rate of pressure rise. Time to failure was compared between groups by log-rank tests. Systolic shortening of the circumflex coronary artery failed at a similar median time point in both groups (30 minutes in the group with single-vessel stenosis and hemodilution versus 40 minutes in the group with multivessel stenosis and hemodilution). Systolic shortening of the left anterior descending artery (80 versus 50 minutes), mean arterial pressure (70 versus 50 minutes), and maximum left ventricular rate of pressure rise (70 versus 40 minutes), however, failed significantly later (p < 0.01) in animals with single circumflex coronary artery stenosis. A marked increase (+50%) in systolic shortening of the left anterior descending artery was observed during hemodilution only in the circumflex coronary artery stenosis group. The better hemodilution tolerance in the circumflex coronary artery stenosis group may be explained by the compensatory increase in myocardial contractile function in non-coronary flow-compromised myocardium, which seems to be crucial for global cardiovascular stability during hemodilution in the presence of coronary stenoses.