The effects of a subsaturating, long treatment (24 h) dose of a highly purified cloned subspecies of human leukocyte interferon (IFN-alpha A) on vesicular stomatitis virus (VSV) primary macromolecular synthesis in tsG41-infected human amnion U cells were examined. IFN-alpha A, under these conditions, was found to inhibit primary VSV protein synthesis ten-fold while producing no detectable effect on the amount or integrity of primary viral message transcripts. There was no selective reduction by IFN-alpha A of the VSV G or M proteins.