The effects of unmodified stroma-free hemoglobin (SFHb) and diaspirin cross-linked hemoglobin (DCLHb) on the regional blood circulation and systemic hemodynamics were studied in rats using a radioactive microsphere technique. SFHb and DCLHb increased mean arterial blood pressure without affecting heart rate. SFHb produced a 24.9% decrease in the cardiac output while DCLHb produced an 44.8% increase in the cardiac output. Stroke volume was decreased (-27.3%) by SFHb and increased (+36.4%) by DCLHb. Total peripheral resistance increased with both SFHb and DCLHb. DCLHb increased blood flow to the heart, spleen, stomach, small intestine and skin, and had no effect on blood flow to the brain, kidneys, liver, mesentery, pancreas, caecum, large intestine and musculo-skeletal system. In contrast, in animals infused with SFHb, blood flow decreased to the kidneys, liver and spleen, increased to the heart, small intestine and skin, and had no effect to the brain, caecum, large intestine and musculo-skeletal system. DCLHb had no effect on vascular resistance in any organ except for an increase in the musculo-skeletal system. In contrast, SFHb increased vascular resistance in the kidneys, liver, spleen, skin, mesentery and pancreas, and had no effect on vascular resistance in the musculo-skeletal system, brain, heart, stomach, small intestine, caecum and large intestine. SFHb had no effect on distribution of cardiac output to the brain, gastrointestinal tract (GIT), kidneys, skin, musculo-skeletal and portal system, while DCLHb significantly decreased the percent cardiac output to the musculo-skeletal system. DCLHb did not affect the distribution of cardiac output to the brain, GIT, kidneys, skin and portal system. SFHb and DCLHb increased the percent cardiac output to the heart. It is concluded that similar concentrations and doses of DCLHb and SFHb produce different effects on the regional blood circulation and systemic hemodynamics.