Recombinant DNA-derived murine 7-interferon (rMuIFN-7) was tested in the murine skin multistage carcinogenesis model as a modulator of 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion. Female SENCAR mice were topically initiated with 7,12-dimethylbenz- (a)anthracene and promoted twice weekly with TPA for 20 weeks. Intraperitoneal administration of rMuII N-> 1 day prior to TPA treat ment affected neither the kinetics of papilloma development nor the percentage of mice that developed tumors. However, papilloma multi plicities could be either inhibited or increased depending upon the dose of rMuIFN-7. Papilloma multiplicities for mice receiving 100,500,1000, and 5000 units of rMull N-->were 184, 122, 105, and 84% of TPA control values, respectively. In contrast, twice weekly i.p. treatments of 7,12-dimethylbenz(a)anthracene initiated mice with only rMuIFN-7 for 20 weeks did not promote the development of any tumors. Consequently, TPA functioned as a copromoter in those situations in which combined TPA and IFN-7 treatments elevated papilloma multiplicities. Collec tively, the current study demonstrates that rMuIFN-7 can systemically modulate TPA-dependent promotion in mouse skin.