Decreased cardiac output, coronary blood flow, and systemic oxygen transport in polycythemia are attributed to increased blood viscosity and regarded as potentially harmful. We studied the effects of isovolemic polycythemia on these variables as well as on myocardial oxygen consumption and regional myocardial blood flow in 31 anesthetized dogs, seven with cannulated left main coronary arteries. Measurements were made at rest, during hypoxemia or adenosine infusions, and with aortic stenosis, pacing, or an aorto-atrial fistula. When hematocrit increased from 42% to 66%, it reduced cardiac output by 36% and systemic oxygen transport by 8%; with hypoxemia, cardiac output rose in polycythemic dogs. Normoxemic polycythemia decreased myocardial blood flow by 46% and increased mean coronary resistance by 54%, slightly decreased myocardial oxygen transport and consumption, and did not alter coronary sinus oxygen tension or myocardial oxygen extraction. Cardiac stress, hypoxemia, and adenosine infusion lowered coronary resistance in polycythemic dogs. Left ventricular myocardial oxygen transport was dependent on pressure work and not on arterial oxygen content or hematocrit. With maximal coronary vasodilation, coronary vascular resistance at hematocrits of 66% was 1.5 times that at 42%. Polycythemia per se did not alter the even distribution of flows across the left ventricular wall, but subendocardial underperfusion began at higher perfusion pressures in polycythemic than in normocythemic dogs. We conclude that autoregulation plays a role in regulating flows and oxygen transport in polycythemia. With maximal coronary vasodilation, however, the increased viscosity of polycythemic blood could be an important factor reducing the amount of myocardial blood flow and oxygen transport.