A new prevention strategy for CMV infection was evaluated in our pediatric kidney transplant unit. This approach comprises a pre-emptive therapy, based upon the monitoring of CMV pp67 mRNA in whole blood by the qualitative NASBA, combined with prophylactic CMV-IG in high risk (R−/D+) children. Thirty-one kidney transplant children were followed for six months with serial measurements of CMV pp67 mRNA in the blood. The R−/D+ patients were given prophylactic CMV-IG for the first 16 wk after transplantation. I.v. ganciclovir was administered upon CMV detection by NASBA and was discontinued after two consecutive negative results. CMV infection, detected by NASBA, developed in 11 (35%) recipients: one (33%) of the R+/D− patients and 10 (72%) of the R−/D+ patients. CMV disease developed in 9.6% of the patients (3/31), exclusively in the R−/D+ group. These three patients presented concurrently with CMV viremia and disease. It is noteworthy that two of the three patients could not receive a complete course of CMV-IG, and one of the latter two subjects had been treated for acute rejection 15 days before CMV infection. Ganciclovir was given for the 11 cases of primary infection, and for three cases of relapsed CMV infection. pp67 NASBA-based pre-emptive ganciclovir therapy, combined with prophylactic CMV-IG in high-risk patients leads to a lower rate of CMV disease, as long as a complete course of CMV-IG has been administered and ganciclovir is given during the period of treatment for acute rejection in high-risk populations.