We have prospectively analyzed cellular immune reconstitution (IR) in 63 consecutive pediatric patients with beta thalassemia major who underwent an HLA matched related allogeneic bone marrow transplant (BMT). Samples from bone marrow graft and posttransplant peripheral blood samples from recipients at specified time points were assessed for IR of cellular subsets. The median age of the cohort was 7 years, and there were 37 (59%) males. A CD34 cell dose above the median value of 7.3 x 10(6)/kg had a lower incidence of bacterial (P = .003) and fungal (P = .003) infections in the posttransplant period, and was not associated with an increased risk of graft-versus-host disease (GVHD). Among cases that did develop grade II-IV GVHD the absolute CD8 (116 versus 52 cells/microL, P = .012), CD8 naïve (74 versus 9 cells/microL, P = .005), and CD8 memory counts (44 versus 21 cells/microL, P = .010) were significantly higher on day 15. Fifteen patients (24%) rejected their graft (7 primary and 8 secondary). The day 28 natural killer (NK) cell count was significantly associated with secondary graft rejection, event-free survival (EFS), and overall survival (OS) (P = .044, .013, and .034, respectively). On a multivariate analysis, patients with a day 28 NK cell count below the median value of 142/microL had a significantly higher rejection rate (hazard ratio [HR] = 11.1, P = .038) and a lower EFS (HR = 16.3, P = .034).