An adult Puerto Rican male is described who developed an acute hemolytic episode following the infusion of three units of stored autologous red cells. The acute episode was associated with the presence of numerous red cells containing Heinz bodies. Investigation of his red cells revealed a markedly decreased level of the enzyme glutathione peroxidase. Examination of family members revealed moderately decreased levels of red cell glutathione peroxidase activity in both parents and in a sibling suggesting an autosomal recessive mode of inheritance. Metabolic studies on the erythrocytes from this patient revealed a normal level of hexose monophosphate shunt activity under basal conditions but a lack of normal activation of this pathway in the presence of hydrogen peroxide. The results of these studies support the concept that this enzyme, glutathione peroxidase, plays a major role in mediating the normal red cell response to the presence of peroxides.