The frequent association of infection with crises in sickle-cell anemia has long been known, and patients with sickle-cell anemia have been considered unduly susceptible to infection. Furthermore, transfusion reactions occur with unusual frequency in patients with sickle cell anemia. Two patients are described in whom crises were precipitated by blood transfusion. In one, a crisis with abdominal and joint pains and hemolysis of the patient''s sickle cells occurred. In the other, a painful crisis occurred, the transfused normal cells exhibiting a normal survival time. These crises were attributed to pyrogenic reactions. The mechanism whereby fever may precipitate a crisis is discussed. Anemia, increase in temperature, and a fall in pH, increase the dissociation of oxyhemoglobin. In turn, sickling is enhanced and the blood viscosity increased, leading to erythrostasis and "thrombotic" episodes. If this interpretation be accepted, it follows that in the treatment of crises considerable attention should be paid to lowering fever.