Techniques for assay of in vitro lymphocyte transformation (LTF) were used with varicella-zoster virus (VZV) as the antigen to study the temporal characteristics of the VZV-specific cellular immune response in children with varicella and in normal subjects with a history of the illness. The LTF response in children with only vesicular eruptions was prompt, and individual peak activity was detected within one to two weeks after the onset of illness, followed by a gradual decrease of the activity to lower levels. Patients with a complication of meningoencephalitis showed a marked delay in the development of peak activity. No consistent defference in the development of complement-fixing antibody to VZV was observed in these patients with different clinical manifestations. The LTF response of normal subjects with remote clinical evidence of varicella was characterized by occasional high activity, a finding that suggests reinfection with VZV. These observations provide additional evidence that the specific cellular immune response is heavily involved in the pathogenesis of VZV infection.