Twenty-one adult patients with acute leukemia who underwent autologous blood stem cell transplantation (ABSCT) and who received acyclovir during the first 6 months after transplant to prevent varicella zoster virus (VZV) infection were studied retrospectively to determine the incidence and outcome of VZV infection after ABSCT. The cumulative risk of VZV infection was 32% by 1 year after transplant. No patient developed VZV while on prophylactic acyclovir but five (24%) had localized herpes zoster within 1 month of acyclovir withdrawal. There were no deaths related to VZV infection and only one patient had disseminated disease and post-herpetic neuralgia. These preliminary results suggest that the incidence and outcome of VZV infection after ABSCT largely parallel those reported in marrow transplant patients and that long-term acyclovir prophylaxis delays but does not prevent VZV infection. Prophylaxis of VZV infection after ABSCT requires new therapeutic approaches.