In this report, the contribution of PKR to the IFN-γ mediated inhibition of VSV replication in neurons was examined. IFN-γ treatment of NB41A3 murine neuroblastoma cells resulted in the reduced expression of VSV protein during infection. PKR was found to be modestly upregulated in NB41A3 cells following IFN-γ treatment. The phosphorylation state of PKR and its downstream target, eIF2α, were unaffected by either IFN-γ or VSV infection. Inhibition of PKR through the use of 2-aminopurine or the expression of the Influenza A NS1 gene had no effect on the ability of IFN-γ to inhibit the replication of VSV in vitro. These data indicate that endogenously expressed PKR is not required for the IFN-γ mediated inhibition of VSV replication in NB41A3 neuroblastoma cells.