Human and murine neuroblastoma cell lines were infected in vitro with varicella-zoster virus (VZV). Infected human neuroblastoma cells (IMR-32) supported the synthesis of abundant viral antigens as detected by indirect immunoperoxidase labeling using human serum rich in anti-VZV antibodies and did not survive the infection. In situ hybridization (ISH) with VZV-cloned probes revealed a strong hybridization signal in these infected cells. During cultivation, the virus was released in the culture medium, and viral polypeptides were revealed by Western blotting of infected cells, using either a monoclonal anti-gpl antibody or a rabbit antiserum. All these findings indicate that IMR-32 cells support a productive and lytic infection by VZV, whether infected by cell-free virus or by cocultivation with infected cells. Murine neuroblastoma cells (neuro-2A) survived VZV infection and did not produce any infectious virus. No VZVspecific proteins were detected in infected cells either by immunolabeling or by Western blotting. However, viral nucleic acids could be detected by ISH, indicating that mouse neuroblastoma cells displayed a nonproductive, nonlytic infection. Infected neuro-2A cells have been examined by ISH using probes corresponding to immediate early (IE) genes 4,62, and 63 and late (L) gene 31 encoding gpII. A strong hybridization signal was detected when infected cells were probed with a fragment containing the IE genes 62 and 63. Lower levels of hybridization were detected with the other probes, corresponding to IE or L genes. These systems allow comparative molecular analysis of persistent and acute infection of nerve cells by VZV.