The differential and cell type specific expression of various murine IFN alpha genes and IFN beta was examined by S1 nuclease protection assays in M-CSF cultured C57BL/6 mouse bone marrow macrophages and L929 fibroblasts. In Newcastle disease virus (NDV) induced macrophages, IFN beta, alpha 2, alpha 4, and alpha 1 mRNAs were the predominant species, whereas IFN alpha 6 and alpha 9 transcripts accounted for only 5% of total IFN alpha mRNAs. In L929 cells, only IFN beta, alpha 2, and alpha 4 genes were expressed efficiently following NDV induction and IFN alpha 9 mRNA was always below detectable level. Induction of macrophages with the synthetic inducer 10-carboxymethyl-9-acridanone resulted in small amounts of IFN alpha 2, alpha 4, and alpha 6 mRNAs and the IFN beta mRNA level was about 100-fold higher. Macrophages and L929 cells especially differed in the kinetics of IFN gene induction in that macrophages showed a much earlier transient expression of all IFN mRNA species. Additionally, IFN transcripts were degraded much faster in macrophage cultures than in L929cells. The IFN response of macrophages is thus characterized by a highly efficient control, providing a rapid onset and a rapid decline of IFN production, which limits release of IFN to a short time interval.