Acute thermal injury of rat skin produces an early, acute hemoglobinemia that is associated with the presence in blood of osmotically fragile red cells (RBC) that do not contain on their surfaces measurable amounts of complement components. The hemoglobinemia and the appearance in blood of osmotically fragile RBC appear to be the result of complement activation, which leads to oxygen radical production by neutrophils and damage of RBC. This has been demonstrated in vitro as well as in vivo by the ability of antioxidant interventions or neutrophil or complement depletion procedures to prevent the appearance of osmotically fragile RBC and the release of hemoglobin. These data may be relevant to the complications of hemoglobinemia and hemoglobinuria accompanying thermal injury in humans.