The clinical spectrum of hemolytic anemia as a consequence of oxidant stress in black children deficient in erythrocyte glucose-6-phosphate dehydrogenase (G-6-PD) has not been well described in the pediatric literature. During a 3 1/2-year period 14 hospitalized black G-6-PD-deficient children with moderate to severe hemolytic reactions were studied. The vast majority (13/14) were boys and were less than 3 years of age. Nine of the patients required blood transfusion. Eleven of the 14 episodes occurred with infection (five bacterial, six viral); those children with viral syndromes tended to have more severe hemolysis. Naphthalene was responsible for three episodes, but oxidant drugs were implicated in no instances. Findings on the blood smears of most subjects included irregular dense misshapen erythrocytes with asymmetrical distribution of hemoglobin and an adjacent membrane-bound clear zone ("eccentrocytes"). It is concluded that hemolytic reactions in the black G-6-PD-deficient child may be severe, are most commonly associated with infection, and are frequently characterized by distinctive erythrocyte morphology.