Severe anemia is a major cause of death in falciparum malaria. Blood transfusion increases survival in humans and in animal models of this disease. Because of logistic constraints and viral contamination of the blood supply, transfusions are frequently not practical in endemic regions. Modified hemoglobin is an effective O2 carrier in hemorrhagic shock. It is free of infectious contamination, may not require refrigeration, and because of its nitric oxide scavenging and small size, may have pharmacologic benefits in malaria. The effects of transfusions of modified hemoglobin in rats with high-grade parasitemia were evaluated. Modified hemoglobin decreased lactic acidosis and corrected anemia as well as transfusions with red blood cells; these findings may correlate with improved survival and suggest a possible proerythropoietic effect. Further study of this novel therapy is warranted.