We investigated the effects of piroxicam, a cyclooxygenase inhibitor, and esculetin, a lipoxygenase inhibitor, on 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis in female rats. Seven days after receiving a 5-mg dose of DMBA, rats were fed either a high-fat (20% soybean oil) or low-fat (0.5% soybean oil) diet. One third of the rats received diets containing 0.01% piroxicam and one third received diets containing 0.03% esculetin. Esculetin significantly inhibited mammary tumorigenesis and tumor proliferation in the rats fed the high-fat and the low-fat diets. Piroxicam had no inhibitory effect. Our findings indicate that DMBA-induced mammary tumorigenesis is affected by lipoxygenase products rather than by cyclooxygenase products.