At least three different enzymes involved in the regulation of protein synthesis are induced in a variety of cells by interferon (IFN)1-5. Sensitive assays for these enzymes have been developed and used to establish the specificity, dose dependence and time course of their induction by IFN 5-8. One of these enzymes, the oligo-isoadenylate synthetase E, whose product (2′-5′)pppApApA9 activates the latent ribonuclease F10-11, is increased over 50-fold after IFN treatment. We describe here the assay for an mRNA from IFN-treated mouse L cells, that produces oligo-isoadenylate synthetase activity when injected into Xenopus oocytes. This mRNA is found in the cells only after exposure to IFN. The mRNA increases in mouse L cells with the same time course as the enzyme activity itself. In particular, there is a 3-h lag period between IFN addition and the onset of enzyme and mRNA accumulation. Using anti-IFN antibodies, we show that during this lag period the continued interaction of IFN with the cells is necessary for the full induction of the oligo-isoadenylate synthetase.