The regulation of interferon action in human fibroblasts will be investigated. Our studies (Gupta et al., 1979; Rubin and Gupta, 1980) on the induction of specific gene products in human fibroblasts in relation to interferon action have revealed that (1) the induction of specific gene products by interferon is followed by a shut-off, thus indicating that the cellular response to interferon is subject to regulation, and (2) the antiviral action of interferon in human cells can be greatly amplified by appropriate treatment with actinomycin D or DRB (5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole). This regulation and amplification of interferon action will be investigated: whether this regulation is due to a modulation of cellular responsiveness to interferon or due to the production of certain inhibitor(s) of interferon action; to test the specificity of this regulatory phenomenon; to study the cellular recovery from hyporesponsiveness to interferon; and the maintenance of the antiviral state in the continued presence of interferon. Studies on the amplification of the antiviral action of interferon by actinomycin D (and DRB) will include: study of the kinetics of the amplification phenomenon; experiments to test for 'superinduction' of specific interferon-inducible proteins and enzymes (2',5'-oligoadenylate synthetase and protein kinase), and to test for any effect on their stability; studies to test whether this amplification requires de novo protein synthesis; and to test the effect of various other inhibitors of RNA synthesis.