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Summary In an organotypic nerve cell culture system, all cells in both the central and the peripheral nervous system (CNS, PNS) components supported replication of herpes simplex virus types 1 and 2 (HSV 1, HSV 2). In HSV 1 infection, cellular response was particularly characterized by the formation of small syncytia (which involved neurons) and by the presence of bundles of interwoven fine filaments within the nuclei of infected cells. In HSV 2 infection, groups of parallel tubules characteristically formed in the nuclei of infected cells. All cells in the CNS or PNS succumbed to virus infection, some within 24 h (e.g. oligodendrocytes) and others after 48 h (e.g. neurons), with the exception of astrocytes. Although among the first cells to develop virus nucleocapsids in their nuclei, astrocytes became swollen and filled with increased numbers of bundles of glial filaments within 24 h after infection; by 48 h the actual number of astrocytes was increased by as much as three- to fourfold over the number in controls. The results suggest that astrocytes may have a unique mechanism which modifies virus infection and the cells not only survive, but can also become reactive.