We report here an in vitro model of neuronal infection by varicella-zoster virus (VZV). Such a model has been achieved by using dissociated adult rat dorsal root ganglia cells infected by cocultivation with VZV-infected MRC5 cells or with cell-free virus. Indirect VZV immunolabeling, in situ hybridization, and neuron-specific immunolabeling demonstrated that VZV infection occurred selectively in neurons. VZV-specific immunolabeling detected a few neurons 1 or 2 days postinfection but not later. Genome detection using cloned VZV DNA probes revealed a hybridization signal primarily with RNA. Within 1 to 6 days postinfection, a progressive increase of VZV-specific hybridization was observed in up to 50% of the neurons. RNAs corresponding to immediate-early, early, and late genes were found, and transcripts of immediate-early gene 63 were particularly abundant.