In cells derived from congenic BALB.A2G-Mx mice carrying the resistance gene Mx, but not in cells from BALB/c mice lacking Mx, mouse interferons alpha and beta induced the synthesis of a unique cellular protein that was associated with an efficient antiviral state with selectivity for influenza viruses. In contrast, native or recombinant mouse interferon gamma failed to efficiently protect Mx-bearing cells against influenza viruses and did not noticeably induce the synthesis of the Mx-associated protein, although interferon gamma was as effective as interferons alpha and beta in protecting BALB.A2G-Mx and BALB/c cells against the rhabdovirus VSV. These results demonstrate that different types of interferons differentially regulate the expression of the Mx gene and thereby induce distinct antiviral states.