This study reports the modulating effects of resistant starch (RS) and the fat-soluble vitamins A or E, alone or in combination, on initiation of preneoplastic lesions in rat colon aberrant crypt foci (ACF) induced by 1,2-dimethylhy-drazine. One group of male Sprague-Dawley rats was fed a basic diet and five groups were fed experimental diets supplemented with 25% RS, 200 IU vitamin A, 5 IU vitamin E, 25% RS + 200 IU vitamin A, or 25% RS + 5 IU vitamin E for four weeks. After induction by 1,2-dimethylhydrazine, all the animals were fed basic diets for four more weeks before sacrifice. Compared with the basic diet, only the vitamin A-supplemented diet significantly reduced the incidence of ACF. The vitamins incorporated in the animals' diets increased the vitamin concentrations in hepatic and colonic cells compared with the animals fed the basic diet. The preventive effect of vitamin A seems to be due to a direct effect on colonic epithelial cells. The three diets supplemented with RS significantly decreased cecal pH and bacterial beta-glucuronidase activity and increased cecal weight and fecal output. The retrograde high-amylose maize, type 3, used in this study does not significantly decrease ACF. This RS has an effect on the colon similar to that of nonstarch polysaccharides. Neither biochemistry nor four weeks of dietary supplementation is likely sufficient for adaptation of the rat colonic flora.