Although reovirus infection may lead to changes in endocrine function in vivo, little is known about the precise interaction of reovirus with endocrine cells. In this study we have examined the effects of reovirus infection on two types of endocrine cells, GH4C1 cells and RINm5F cells. Both type 1 reovirus and type 3 reovirus infect the two cells lines and appear to grow equally well. Viral replication occurred within the first 24 h following infection after which viral titers remained stable for 3 days. By 48-72 h after viral infection, substantial cytopathic effects were noted in RINm5F cells infected with both type 1 and type 3 reovirus. In GH4C1 cells, type 3 reovirus was most effective in producing cell death, and type 1 reovirus was significantly less cytotoxic despite a similar viral titer. Only type 1 reovirus caused a specific inhibition of overall protein and DNA synthesis, and this occurred only in the RINm5F cells. Over the time course studied, GH4C1 cells successfully infected with type 1 reovirus demonstrated no cytopathic effects, and only minimal alterations in cellular function were noted. Intracellular insulin content and insulin secretion, a "luxury function" of the RINm5F cells, were also surprisingly well maintained in the first 48 h after viral infection. In addition, virally infected cells were able to respond to glyceraldehyde, an insulin secretagogue, although the response appeared to be somewhat blunted compared to that of control cells. These results suggest that viral infection of endocrine cells results in specific alterations that depend on the nature of the infecting virus. In addition, the cellular environment of the host cell may be an important determinant in the outcome of viral infection.