Benzoyl peroxide (BPO), a free radical generating compound, is widely used in topical medications prescribed for acne vulgaris and in cosmetic products. It has been shown to possess tumor-promoting activity in murine skin initiated with chemical carcinogens such as 7,12-dimethylbenz(a)anthracene (DMBA). In the present study we assessed the effect of the antioxidants nordihydroguaiaretic acid (NDGA) and diallyl sulfide (DAS) against BPO-mediated tumor promotion in murine skin. Pretreatment of Sencar mice with NDGA and DAS prior to skin application of BPO resulted in a time- and dose-dependent inhibition of epidermal ODC induction caused by BPO. Tumor initiation was achieved by a single topical application of DMBA (10 μg/animal) to Sencar mice. Ten days later tumor promotion was begun by twice-weekly topical application of BPO (20 mg/animal). The anticarcinogenic effects of NDGA (25 μmol/mouse) and DAS (20 μmol/mouse) were evaluated by administering these agents topically 60 min prior to each BPO application. After 26 weeks on test, the number of benign papillomas/ mouse were 0.10 ± 0.07 and 2.15 ± 0.30 in the NDGA and DAS pretreated group of animals as compared to 4.40 ± 1.14 in animals receiving BPO alone. After 51 weeks on test, the number of squamous cell carcinomas/mouse were 0.00 ± 0.00, 0.35 ± 0.10 in the NDGA and DAS pretreated group of animals as compared to 0.65 ± 0.12 in animals receiving BPO alone. From these data we suggest that the antioxidants NDGA and DAS can abrogate the tumor-promoting effects of BPO in murine skin and that NDGA is substantially more effective than DAS in this regard. © 1990.