Acute splenic sequestration crisis (ASSC) in children with various forms of sickle cell disease can result in life-threatening circulatory collapse due to the loss of circulating blood volume. Over a 6-year period we have treated 12 patients ranging in age from 5 1/2 months to 7 years presenting with acute sequestration crisis. Eleven had homozygous sickle cell disease and the other had sickle-thalassemia. One patient died of acute circulatory collapse. Eight patients underwent splenectomy after a major episode of sequestration with no serious infectious complications up to 5 years following splenectomy. Three patients with minor episodes have been followed with no recurrences. To foster early detection of this potentially lethal complication of sickle cell disease, an educational program in our Comprehensive Sickle Cell Center instructs the parents to examine the spleen and bring their child in for evaluation if the spleen enlarges. A newly developed videotape describes the common symptoms of ASSC and illustrates the technique of palpating the spleen. With early detection of sickle cell disease by neonatal screening and the educational program, the morbidity and mortality from this complication of sickle cell disease can be reduced.