Summary Ten cases of sudden death occurring in children with sickle cell anemia are reported. Seven of the deaths occurred within 45 minutes of hospitalization. The clinical picture common to the entire group was extreme pallor, weakness and lethargy, shocklike appearance, tachycardia, and cold clammy skin. The most striking necropsy finding in the 7 patients autopsied was congestion of the internal organs with sickled erythrocytes. A possible mechanism of stasis of red blood cells in the spleen, liver sinusoids, and/or splanchnic capillaries with peripheral vascular collapse and cerebral anoxia is proposed to explain sudden death in infants and small children who are already debilitated by anemia, hemolysis, infection, and the like. In order to prevent a fatal outcome it is often necessary to provide emergency measures such as immediate transfusion of whole blood or packed erythrocytes, oxygen inhalation, and antibiotics for associated infections.