Analysis of gene expression in peripheral blood lymphocytes is of especial interest because it could reflect physiological conditions. We have examined the expression and compared the relative amounts of specific mRNAs for interferons (IFN-α and IFN-β), tumor necrosis factor-α (TNF-α) and interferon regulatory factors (IRF-1 and IRF-2) from interferon primed and Sendai virus induced peripheral blood leukocytes. Results obtained showed that IRF-1 was highly inducible by IFN treatment, IFN-α, TNF-α and IRF-2 were weakly induced by IFN treatment, and IFN-β was not inducible by priming the cells with recombinant human IFN-α2B. The IFN-α, IFN-β, IRF-2 and TNF-α transcripts increased upon viral infection. The IRF-1 mRNA was rapidly induced by IFN treatment and decreased after Sendai virus infection. Our results show that, in peripheral blood lymphocytes, IFN-α and -β genes have a different response to IFN induction, thus suggesting different regulatory mechanisms for IFN induction of type I IFN genes in peripheral blood lymphocytes.