We characterized the surface phenotype of B cells from HIV+ children in order to better understand the biology of B cell dysregulation. Twenty-nine HIV-infected, twenty-one exposed, and nineteen age-matched control children were studied for expression of CD5, CD10, CD21, CD23, CD25, CD62L, CD71, and CD69. We conclude that, despite persistent high immunoglobulin levels, total B cells decreased as HIV disease progressed, with selective decreases in CD62L+ and CD23+ B cells. This resulted in an increased proportion of usually minor subpopulations of CD62L- and CD23-negative B cells. We did not find significantly altered B cell expression of other activation/immaturity antigens. This suggests an absolute decrease in a subset of antigen-responsive B cells and a disproportionate increase in a subset of hyperstimulated B cells. These findings provide a biological basis for the paradoxical generalized B cell hyperactivity and specific immune unresponsiveness that are characteristic of HIV infection in children.