The relative capacity of germfree mice to respond to virus stimulation with interferon production in vivo was studied. Germfree CFW mice responded to intravenously inoculated Newcastle Disease virus with a pattern of serum interferon production similar to that of conventional mice. The baseline inhibitory activity of serums from unstimulated control germfree and unstimulated control conventional mice were the same. There was some indication that the spleen and liver interferon responses of germfree mice may be higher than those of conventional mice. Such higher responses in germfree mice might be due to higher storage levels of preformed interferon or of interferon precursors in the germfree mice because of their comparatively pristine condition.