Primary varicella-zoster virus (VZV) infections following organ transplantation may cause significant morbidity. We examined the safety and immunogenicity of Varivax after transplantation as a potential prophylactic tool. Pediatric liver and intestine transplant recipients without history of chickenpox received one dose of Varivax. VZV humoral and cellular immunity were assessed before and > or =12 weeks after vaccination. Adverse events (AE) and management of exposure to wild type VZV were monitored. Sixteen VZV-naïve subjects, 13-76 months of age, at 257-2045 days after transplantation were immunized. Five children developed mild local AE of short duration. Four subjects developed fever and four developed non-injection site rashes, three of whom received acyclovir. Liver enzymes did not increase during the month after vaccination. Eighty-seven percent and 86% of children developed humoral and cellular immunity, respectively. There were five reported exposures to varicella in four children, none of which resulted in chickenpox. One subject received VZV-immunoglobulin and another subject with liver enzyme elevations after exposure received acyclovir; all remained asymptomatic. Varivax was safe and immunogenic in pediatric liver and intestine transplant recipients. Larger studies are needed to establish the efficacy and role of varicella vaccination after transplantation.