It has become increasingly evident that both quantity and quality of dietary lipid can influence the developmental course of several major forms of cancer in experimental animals. Using the hairless mouse-ultraviolet (UV) model, we had previously demonstrated that unsaturated lipid compared to equivalent levels of hydrogenated lipid enhanced photocarcinogenesis with respect to both tumor latency and multiplicity. In the present study using the same model, we have examined the effect of unsaturated lipid level and antioxidants upon epidermal lipid peroxidation and UV carcinogenesis. Sixteen groups of 45 animals each were used in the study, representing all combinations of three design variables: (a) a semipurified diet containing 4, 2, or 0.75% corn oil or 4% soybean oil; (b) 2% (w/w) antioxidant supplement or no supplementation; and (c) an escalating regimen of UV radiation to a cumulative dose of 70 J/cm2 or no irradiation. The nonirradiated groups served as nutritional controls and as subjects for epidermal lipid peroxidation measurements. An approximate linear relationship between lipid level and tumor latency was observed, with 4% levels of unsaturated lipid producing maximum enhancement of photocarcinogenesis. Furthermore with increasing lipid level the numbers of tumors per animal increased. Antioxidants caused significant increases in tumor latency and decreases in tumor multiplicity but only at the highest lipid level used in these studies. Thiobarbituric acid values of epidermal homogenates also increased in relation to the level of dietary lipid intake. Epidermal thiobarbituric acid values from antioxidant supplemented animals were significantly lower regardless of lipid intake levels. From these data we conclude that (a) dietary lipid level has a direct effect upon the carcinogenic response to UV both in regard to tumor latency and tumor multiplicity; (b) antioxidants produce an inhibitory effect almost equal to the degree of exacerbation of carcinogenesis evoked by increasing lipid levels, at least for the range studied; and (c) dietarily administered antioxidants inhibit the formation of epidermal thiobarbituric acid reacting materials. These data strongly imply that free radical reactions, specifically lipid peroxidation, play a role in at least a part of the photocarcinogenic response.