Summary: The action of interferon in inhibiting either visible virus effect on cells or viral multiplication is intracellular. The evidence suggests that very soon after its adsorption interferon acts to delay virus synthesis in cells naturally susceptible to virus as well as those naturally insusceptible, even when interferon is added after viral ribonucleic acid (RNA) adsorption to cells is completed. This action occurs beyond the point of cellular adsorption, penetration, and removal of virus protein without gross effect upon virus release. It further appears that interferon does not block intracellular sites of attachment for viral multiplication, nor does its effect depend upon direct inactivation of parental viral RNA. Interferons produced in the allantoic sac of chicken embryos by a myxovirus (influenza A) or an arthropod-borne virus (Japanese encephalitis) had similar inhibitory effects on chicken embryo cells against Western equine encephalitis virus as well as against the RNA extracted from poliovirus Types I and II. Avian interferon had no detectable effect on susceptibility of HeLa cells to poliovirus RNA.