Varicella-zoster virus (VZV) DNA was detected in mononuclear cells (MNC) of 7 humans with acute zoster 1-23 days after the onset of skin lesions. To further study the interaction of VZV with human MNC, cells obtained from seropositive normal donors were infected with VZV and analyzed for the presence of viral DNA and proteins. VZV-DNA was detected in T, B, and OKM 1 (monocyte-macrophage) positive cells, and virus-specific proteins were demonstrated by indirect immunofluorescence and immunoprecipitation. Hybridization studies revealed that VZV-DNA did not replicate in human MNC.