Intramolecularly (alpha-alpha) cross-linked hemoglobin has been reported to have oxygen transport properties similar to those of whole blood. The present study evaluated the efficacy of diaspirin alpha-alpha cross-linked hemoglobin solution as a resuscitation fluid, with heart rate, mean arterial pressure, and transcutaneous oxygen tension as the study parameters. Rats were bled and approximately one third of their total blood volume (20 ml/kg) was removed while they were anesthetized; they were then resuscitated with 14% hemoglobin solution. Animals that received either 10 mg/kg (n = 10) or 20 mg/kg (n = 10) of hemoglobin solution responded quickly and positively to the infusions: mean arterial pressure (which had dropped to less than 40% of prehemorrhage levels) returned to baseline within 2 minutes of initiating infusion; by 4 minutes, the mean arterial pressures of the hemoglobin-infused groups were significantly higher (p less than or equal to 0.05) than those in both the autologous shed blood (n = 8) and lactated Ringer's (n = 10) groups. The heart rate and transcutaneous oxygen tension responses in both the half-volume and full-volume replacement hemoglobin groups matched the response to autologous shed blood throughout the hour of observation. The favorable hemodynamic response to infusion of cross-linked hemoglobin solution after hemorrhage suggests that this material is comparable to autologous shed blood and superior to lactated Ringer's solution as a resuscitative fluid as assessed in this model.