Recombinant human interferon- ser¹⁷ (IFN- ser¹⁷), a cytokine that exhibits both antiviral and antiproliferative activity against a wide variety of cell types, causes a time- and dose-dependent inhibition of monolayer growth and of the expression of the c-myc proto-oncogene in DLD-l Clone A human colon-carcinoma cells. The suppression of c-myc expression mediated by IFN- ser¹⁷ is due to a posttranscriptional destabilization of c-myc mRNA rather than to an inhibition of c-myc mRNA transcription. There is evidence suggesting that the selective reduction in the half-life of c-myc mRNA in IFN- ser¹⁷-treated cells occurs through an increase in the activity of the 2,5-oligoadenylate synthetase/RNase L [2,5-oligo (A) synthetase] pathway in DLD-1 Clone A cells. Cotreatment of these cells with IFN- ser¹⁷ and the anticancer agentN-methylformamide leads to the partial abrogation of 2,5-oligo (A) synthetase activity and the stabilization of c-myc mRNA. These findings suggest that there is a correlation between the IFN- ser¹⁷-mediated suppression of c-myc expression and the induction of 2,5-oligo (A) synthetase activity in DLD-1 clone A cells.