BACKGROUND.: Vaccination against Epstein-Barr virus (EBV), inducing an antibody response to the envelope glycoprotein gp350, might protect EBV-negative children with chronic kidney disease from lymphoproliferative disease after transplantation. METHODS.: A phase I trial recruited children with chronic kidney disease to two successive cohorts given three injections of 12.5 microg (n=6) and 25 microg (n=10) recombinant gp350/alhydrogel vaccine over 6 to 8 weeks. RESULTS.: One in each cohort acquired wild EBV before the week 28 evaluation. Both doses were similarly immunogenic, inducing an IgG response in all 13 evaluable patients. Neutralizing antibodies were detected in four recipients (1/4 in the 12.5 microg and 3/9 in the 25 microg cohort). Median time from first vaccination to transplantation was 24 weeks. Immune responses declined rapidly and were unlikely to affect posttransplant events. DISCUSSION.: The vaccine was immunogenic but a prolonged vaccine schedule up to time of transplantation or improved adjuvants are required in future trials to reduce posttransplant EBV load and risk of lymphoproliferative disease.