Since Plasmodium falciparum malaria is a frequent cause of anemia among African children, and blood transfusions, unscreened for human immunodeficiency virus (HIV) antibody, are used frequently in the treatment of children with severe malaria, the relationships between malaria, transfusions, and HIV seropositivity were investigated in a pediatric population in Kinshasa, Zaire. In a cross-sectional survey of 167 hospitalized children, 112 (67%) had malaria, 78 (47%) had received transfusions during the current hospitalization, and 21 (13%) were HIV seropositive. Ten of the 11 seropositive malaria patients had received transfusions during the current hospitalization; pretransfusion specimens were available for four of these children and were seronegative. Of all blood transfusions, 87% were administered to malaria patients, and there was a strong dose-response association between transfusions and HIV seropositivity. A review of 1000 emergency ward records demonstrated that 69% of transfusions were administered to malaria patients, and 97% of children who received transfusions had pretransfusion hematocrits of 0.25 or less (≤25%). The treatment of malaria with blood transfusions is an important factor in the exposure of Kinshasa children to HIV infection.