Fried ground beef contains substances that inhibit mutagenesis in bacteria and the initiation of epidermal carcinogenesis in mice by 7,12-dimethylbenz [a]anthracene (DMBA). The inhibitors apparently act at least in part via inhibition of cytochrome P-450 activity. A highly purified fraction that inhibited cytochrome P-450 activity in vitro was isolated by HPLC and characterized by GC-MS, and by UV and proton NMR spectroscopy. The fraction contained four isomeric derivatives of linoleic acid each containing a conjugated double-bond system (designated CLA). Synthetically prepared CLA (containing all four isomers) was tested for anti-initiation activity in the two-stage mouse epidermal carcinogenesis system. Seven days, 3 days and 5 min prior to DMBA application, CLA was applied at doses of 20, 20 and 10 mg respectively. Control mice were treated similarly with linoleic acid or solvent (acetone). One week after initiation, and twice weekly thereafter, all mice were treated with 12-O-tetradecanoylphorbol-13-acetate to effect tumor promotion. There was no difference in tumor incidence or yield between linoleic acid-treated mice and solvent-treated control mice. By contrast, the CLA-treated mice developed only about half as many papillomas and exhibited a lower tumor incidence compared with the control mice.