Diet-induced changes in serum cholesterol levels and their relationship to mammary carcinogenesis initiated by 7,12-dimethylbenz[a]anthracene (DMBA) were studied in female Sprague-Dawley rats. DMBA was given to rats subjected to 3 dietary treatments: (1) a semipurified, cholesterol-free diet (SP); (2) the same diet with 1.5% cholesterol and 0.5% bile salts added (CB); (3) diet CB, until administration of DMBA and then switched to diet SP. Tumor yield per rat was increased in rats fed diet CB, but incidence and tumor size were similar among all 3 groups. Rats maintained on diet SP alone had a higher percentage of histologically benign tumors. Hypercholesterolemia of dietary origin appears to enhance slightly chemical carcinogenesis in this model.