The Oka strain of varicella-zoster virus (VZV) was first isolated from vesicles of an otherwise healthy 3-year-old boy with typical varicella. The virus was passaged 11 times in human embryonic lung fibroblasts at 34 degrees C and 12 times in guinea pig embryo fibroblasts (GPEFs) at 37 degrees C. GPEFs were the only nonprimate cells tested in which some degree of viral replication occurred. The resultant virus was temperature sensitive and showed host dependency, measured as better replication in GPEFs than that shown by the parental virus. The passaged virus was used as a candidate varicella vaccine and proved safe and effective for healthy and immunocompromised children. During the follow-up of vaccinated children with acute lymphocytic leukemia, the incidence of herpes zoster (HZ) was significantly lower among children who did not have a rash after vaccination, compared with those who had a rash caused by VZV (6 [2.3%] of 260 vs. 12 [17.1%] of 70, respectively). Because of the pathogenesis of VZV, the incidence of latency and of HZ is predicted to be lower among vaccine recipients than among individuals who have experienced varicella.