The major physiological effects of hemorrhage are hypovolemia and anemia. The administration of an oxygen-carrying plasma expander, such as crystalline hemoglobin solution (CHb), can restore both of these deficits while avoiding many of the logistical problems entailed in the use of blood. The authors have used Chb to treat severe hypovolemia and anemia in separate canine models and found it to be highly effective. CHb acts as a colloid plasma expander to resuscitate intravascular volume in hypovolemia and supplements oxygen-carrying capacity in anemia. CHb can support oxygen transport essentially in the absence of red blood cells. Hemodynamic responses to low P50 CHb, however, suggest that oxygen offloading at the tissue level is compromised by the high oxygen affinity of unmodified CHb. Whereas such oxygen offloading deficits may be compensated for in the chronic situation, they may be of crucial importance in severe trauma where oxygen transport is often limited by arterial desaturation, low cardiac output, maldistribution of perfusion and interstitial water overload. The development of a lower-affinity CHb is, therefore, of the essence.