To determine the effects of blood transfusions on splenic function in older patients with sickle cell anemia, we investigated splenic function in 12 patients who had had cerebrovascular accidents and who were being treated at two collaborating centers using different transfusion protocols. Splenic function was assessed by radionuclide scan and pocked erythrocyte count. Patients were 6 to 18 years of age and had been receiving transfusions for 7 months to 10 years (median 4.2 years). Of the 12 children, five had normal or increased splenic size and function (normal scan and normal or minimally elevated pocked erythrocyte count). All were receiving intensive transfusion therapy, with the aim of maintaining the hemoglobin S level at less than 20%. The other seven patients had abnormal splenic function (absent radionuclide uptake and elevated pocked erythrocyte count); each was receiving less intensive transfusion therapy, with the pretransfusion hemoglobin S level usually at 30% to 40%. No patient developed bacterial septicemia while receiving hypertransfusion therapy. We conclude that splenic function during a long-term transfusion program is variable, depending in part on the "intensity" of transfusion therapy. Apparent splenic involution and fibrosis may be a reversible event in some patients.