Background: This study determined individual organ blood flows and global hemodynamic, oxygen delivery and consumption parameters after normovolemic exchange transfusions with the hemoglobin based oxygen carrier (HBOC)-201 in a lightly anesthetized swine model., Methods: The exchange transfusions were performed as a stepped reduction in blood volume to attain volume exchanges of 10%, 30%, and 50% with a 1:1 replacement with HBOC-201 (n = 8) or oncotically matched 5.9% human serum albumin (HSA, n = 8). Four additional animals served as time controls., Results: There was no change in the regional blood flows in 8 of 9 organs (brain, heart, kidney, liver, pancreas, gall bladder, small intestines, large intestines, and skeletal muscle) after HBOC-201 compared with controls; only skeletal muscle blood flow decreased. In contrast, with HSA, blood flow increased 150% to 200% of baseline in all organs except muscle where blood flow was unchanged. HBOC-201 effectively restored oxygen delivery after these exchanges. The mean arterial pressure increases in the HBOC-201 group were within 15% to 20% of baseline during the initial 10% exchange and similar to controls during subsequent exchanges. Although peak pulmonary arterial pressure increases in the HBOC-201 group were 10 mm Hg to 15 mm Hg above baseline, cardiac index was unchanged. There were no differences in global oxygen consumption, consistent with unchanged regional blood flow and suggests intact physiologic coupling of oxygen delivery and consumption that was unimpaired by local vasoconstriction. This is in contrast to significant changes of increased cardiac index, decreased arterial pressure, decreased oxygen content, and increased oxygen extraction ratio to maintain normal oxygen consumption in the HSA group., Conclusion: Although the use of HBOC-201 caused alterations in systemic (minimal) and pulmonary (modest) pressures, these changes had no consequence on regional organ blood flow.