BACKGROUND Mycophenolate mofetil (MMF) is a new immune suppressive agent, effective in the prevention of acute rejection after renal transplantation. METHODS The study was a retrospective review of records of pediatric renal transplant recipients from 1985 to the present. RESULTS Since October 1995, the immune suppression protocol for pediatric renal transplant recipients at Mayo Eugenio Litta Children's Hospital has included MMF, prednisone, and cyclosporine A. During that time, 19 children and adolescents have received renal allografts, 17 of whom were seropositive for varicella antibody before transplantation, while 2 were seronegative. Varicella infection occurred in 3 of 19 patients (15.8%), all 3 of whom had serologically documented immunity to varicella virus before transplantation. All episodes occurred within 12 months of transplantation. All had generalized vesicular lesions without dermatomal distribution. None of the patients developed fever, respiratory, mucocutaneous, or central nervous system manifestations. All were managed with oral acyclovir, and had an uncomplicated recovery without neuralgia. By contrast, of 74 consecutive patients transplanted before use of MMF, only 1 patient (1.4%) had varicella infection after transplantation (P=0.026). CONCLUSIONS The enhanced immunosuppression achieved with MMF appears to be associated with increased susceptibility to varicella infection.