We have reported a new PEG-modified, hemoglobin-based O₂ carrier (MP4) with novel properties, including a large molecular excluded volume and low p50 (~ 6 mmHg). To evaluate the ability of MP4 to transport O₂, we compared it to PEG-modified albumin (MPA), using the identical chemistry of attachment of PEG chains. The resulting solutions were well matched with respect to all physical properties except that MP4 is an O₂ carrier, while PEG-albumin is not. An additional solution, 10% pentastarch (PS), was matched with the PEG-modified proteins with regard to oncotic activity and viscosity, but does not contain PEG. The model used to evaluate O₂ transport was continuous exchange transfusion in the rat until the hematocrit was virtually unmeasureable. Objective endpoints included survival and the onset of anaerobic metabolism, signaled by acid-base derangement and accumulation of lactic acid. Continuous exchange transfusion of 2.5 blood volumes in rats (n=5 in each treatment group) was carried out over 60 minutes such that the final hematocrit was between 0 and 5% in all animals. Animals were observed for an additional 70 minutes, when survivors were euthanized. Overall survival for the MP4 animals was 100%; no animal that received either PS or MPA survived. The hematocrit at which lactic acid began to rise was approximately 14.8% in both PS and MPA animals, and 7.4% in the animals that received MP4. In all groups, the total hemoglobin was approximately 5 g/dL at this point. We conclude that in spite of its low P50, MP4 effectively substitutes for red blood cell hemoglobin in its ability to oxygenate tissues in extreme hemodilution.