This chapter describes the identification, large-scale production, partial purification, and preliminary characterization of an inducible inhibitor of interferon action that is produced by mouse spleen cells treated with T cell mitogens. The mouse spleen cell supernatant fluid preparations that contain the inhibitor of interferon action also contain immune interferon. The inhibitor can be detected and roughly quantitated by taking advantage of the fact that the inhibitor can be measured in undiluted preparations and, except for highly concentrated inhibitor preparations, the inhibitor activity can be diluted out more rapidly than the interferon activity. The purified inhibitor preparations are shown completely to block the antiviral activity of both mouse fibroblast interferon and mouse immune interferon. The inhibitor does not reverse an established antiviral state but can still completely block the development of antiviral activity when added at up to 3 hr after interferon. The inhibitor has also been shown to block the immunosuppressive activity of exogenously added fibroblast interferon in an in vitro plaque-forming cell response. © 1981, Academic Press, Inc.