Ceftriaxone can be associated with catastrophic immune hemolysis in pediatric patients, particularly those with underlying diseases such as sickle cell disease and human immunodeficiency virus infection. We designed a study to screen for ceftriaxone-induced RBC antibodies in these 2 pediatric populations. The prevalence of anticeftriaxone antibody was 12.5% (8 of 64). Two of these 8 patients with the antibody experienced hemolysis; 1 case was fatal.