The invention relates to novel hemoglobin compositions, particularly novel recombinant mutant hemoglobin compositions, which eliminate or substantially reduce 1) the creation of heart lesions, 2) gastrointestinal discomfort, 3) pressor effects, and 4) endotoxin hypersensitivity associated with the administration of extracellular hemoglobin compositions in various therapeutic applications. Applications described include treatments for anemia, head injury, hemorrhage or hypovolemia, ischemia, cachexia, sickle cell crisis and stroke; enhancing cancer treatments; stimulating hematopoiesis; improving repair of physically damaged tissues; alleviating cardiogenic shock; and shock resuscitation.