Clinical severity of sickle cell anemia (SS) in Africa may not be solely determined by genetic factors. This study evaluated the effects of intensive parental education and adequate clinical care on the course of SS in children in Benin. SS children referred to the National Teaching Hospital in Cotonou were included in the study. Teaching about SS was repeated frequently, emphasizing the importance of keeping clinic appointments, improving the nutrition of the affected children, and instituting antipneumococcal and antimalarial prophylaxis. Frequency and severity of SS-related events, changes in physical growth, frequency of malarial attacks, causes of transfusion, and causes of death were the principal variables assessed. 236 young children with repeated SS-related acute complications were studied from July 1, 1993, to December 31, 1999 (983 patient-years). A marked reduction in the frequency and severity of SS-related acute events was observed. Improvement in general status and physical growth was noted in 184 patients (78%); in addition, 22 of the remaining 52 patients showed similar improvement after remotivating the parents for compliance. There were 10 deaths, primarily in this cohort of 52 patients. Intensive sociomedical intervention can produce sustained clinical improvement in many severely ill SS children in sub-Saharan Africa.