Synthetic erythrocytes (SE) can maintain life with near-normal hemodynamics in rats with hematocrits (Hct) 45% below the lethal levels, as shown when we exchanged virtually all their blood. We compared cardiorespiratory variables between the SE and control animals, which were hemodiluted with 7% albumin, at the 78% exchange level. In addition, SE animals at 92% exchange were compared with the 78% exchange and baseline levels. All our control rats died at Hct above 5% with corresponding oxygen-carrying capacity of 2.65 ml/dl. All SE rats survived, having a final Hct of 2.96% with an oxygen-carrying capacity of 7.05 ml/dl. SE animals maintained normal BP and marginally increased cardiac output, while control animals did not. Vascular resistance of control animals at 78% exchange was reduced to 30%, while in SE animals at 92% exchange, vascular resistance was lowered to 80% of baseline values.