Maternal morbidity and perinatal outcome in 108 pregnancies complicated by sickle cell anemia (hemoglobin SS disease), sickle cell-hemoglobin C disease (hemoglobin SC disease), or sickle cell-beta-thalassemia disease were analyzed. Women given prophylactic red cell transfusions (1973-1982) during pregnancy were matched with historic controls whose care was almost identical except that blood was not given unless indicated (1955 to 1972). In women with hemoglobin SS disease who received prophylactic red cell transfusions, there was a sevenfold reduction in perinatal mortality and negligible maternal morbidity. In pregnancies complicated by hemoglobin SC disease during which transfusions were given, there were no perinatal losses, whereas there were in 18% of women not given transfusions. Maternal morbidity in women given transfusions was negligible; however, half of those not transfused experienced morbidity and, importantly, pulmonary complications were common. Transfusion-related complications included hepatitis and alloimmunization. From these experiences the authors conclude that prophylactic red cell transfusions reduce maternal morbidity and perinatal mortality appreciably, although perinatal morbidity is not eliminated. Transfusion therapy is justifiably started early in pregnancy for women with hemoglobin SS disease; however, transfusions may be withheld until the end of the second trimester for women with hemoglobin SC or sickle cell-beta-thalassemia disease.