Jsb is a high-frequency antigen. Anti-Jsb is a rare alloantibody, and its clinical significance is poorly documented. We report a case in which a 12-year-old boy of Nigerian descent with sickle beta- thalassemia presented with multiple alloantibodies, including a panagglutinin and acute chest syndrome, necessitating the emergent transfusion of five units of phenotype-similar, crossmatchincompatible RBCs, four of which were given during an exchange transfusion. The patient was later found to have anti-Jsb. In addition to routine serologic methods to study the patient's RBCs and plasma, a monocyte monolayer assay (MMA) was performed on the patient's samples obtained 2 and 9 days after transfusion of the Js(b+) RBCs to determine the potential clinical significance of the anti-Jsb. Various laboratory parameters including quantitative hemoglobin fraction analyses were used to monitor for increased RBC destruction. The MMA reactivity of the patient's anti-Jsb increased from 2.3 percent on day 2 after transfusion to strongly positive at 88 percent and 66.5 percent (with and without the addition of fresh serum) 1 week later. MMA reactivity of greater than 5 percent is associated with increased RBC destruction. There was no clinical or laboratory evidence of increased hemolysis above baseline. However, decreased RBC survival was suggested by the relatively brisk decrease of the HbA1 fraction after the transfusions. The current case and others reported in the literature suggest that anti-Jsb may have limited potential for causing overt hemolysis. However, in patients with underlying hematologic disease, even mildly increased RBC destruction may pose problems clinically,and thus transfusion of Js(b+) RBCs should be avoided. In emergent situations, the potential of adverse effects of transfusing incompatible units should be balanced against the risk of withholding transfusion. Family members, especially siblings, should be considered as potential designated donors for patients with antibodies directed against high-frequency antigens. Available reports on anti-Jsb in the literature are also reviewed.