The hematocrit of 12 dogs was reduced from 43 to 30 and then to 20% by bleeding and simultaneous infusion of lactated Ringer''s solution. At each level of anemia, blood volume, heart rate, cardiac output, left and right atrial pressures, left ventricular (LV) work, aortic mean pressure and systemic vascular resistance were at prebleeding values. Pulmonary arterial saturation decreased from 76 to 67 and 50%. LV coronary venous saturation fell from 46 to 31% at hematocrit 30, with no further reduction at hematocrit 20. Electromagnetically measured left coronary mean flow was 120 and 185% of control at hematocrits 30 and 20. Coronary flow reserve, or the ratio of peak increase in flow after 10 s occlusion to preocclusion flow, was 3.8 at hematocrit 43, 3.0 at 30 and 1.9 at 20. The change in ratio was due to increased resting flow with anemia but peak reactive hyperemia flow did not change with hematocrit. Acute normovolemic anemia was not associated with significant changes in cardiac work. Despite lowered blood viscosity, systemic resistance was maintained by vasoconstriction. Systemic O2 availability (cardiac output .times. arterial O2 content) was decreased but uptake was maintained by increased O2 extraction. LV O2 consumption was maintained by maximally increasing the already high myocardial O2 extraction and by increasing coronary flow. At half-normal hematocrit, coronary reserve was compromised significantly, indicating cardiac vulnerability at these levels of anemia, especially if coronary occlusive disease or higher work demands on the heart should coexist.