Pneumococcal polysaccharide (PPS) antibody deficiency occurs in some children immunosuppressed following cardiac transplantation in early childhood. We studied lymphocyte subset populations in these children to identify patterns associated with antibody deficiency, particularly in CD21 + B cells. Lymphocyte surface markers CD3, CD4, CD8, CD19, and CD21 were measured on whole blood by FACS analysis in four patient groups: cardiac transplant patients who did and did not respond to PPS, nontransplanted cardiac patients, and normal controls. Absolute cell numbers were compared with age-related normal ranges. The proportion of children with values below the age-related 25th percentile in each group was compared. Normal controls had significantly more CD3+, CD8+, and CD19+ cells, even when age-related differences were accounted for. Control groups had significantly more CD19 cells than transplant patients and transplanted PPS responders and cardiac controls had more mature B cells (CD21+) than transplanted PPS nonresponders. PPS antibody deficiency following pediatric cardiac transplantation may be related to an immaturity in B cells due to immunosuppression commenced in early childhood.