Cytomegalovirus (CMV), the most significant infectious cause of morbidity following renal transplantation, may be a greater problem for children than for adults due to their relative lack of experience with this virus. Therefore, we prospectively gave Gammagard as prophylaxis to CMV-negative children who received CMV-positive allografts and compared the results to our experience with similar high-risk recipients transplanted prior to our use of intravenous immunoglobulin G (IvIgG). Symptomatic CMV disease developed in 17% of the IvIgG recipients as compared with 71% of the untreated patients (p = 0.01). The CMV infections that did occur in IvIgG recipients developed significantly later than in untreated children (median time of onset after transplantation 2.60 vs. 1.35 months; p < 0.05) and generally were less severe, although 1 IvIgG recipient died despite prophylaxis. IvIgG administration did not affect the frequency of rejection or graft or patient survival. We conclude that IvIgG administration to high-risk pediatric renal transplant recipients may protect against posttransplantation CMV disease and may lessen the severity of infections that do develop in patients who receive it.