Epidemiologic studies have linked the consumption of red meat and the consumption of highly browned meats containing high levels of heterocyclic aromatic amines (HCAs) to increased risk of colorectal cancer or polyps. The present study determined the effects of long-term feeding of beef-containing diets with low and high levels of HCAs (in the context of a low or high beef tallow diet) on a standard 1,2-dimethylhydrazine (DMH)-induced colon tumorigenesis protocol. Very lean beef was cooked by a variety of methods at different temperatures, and the levels of the major HCAs (2-amino-3,8- dimethylimidazo[4,5-f]quinoxaline, 2-amino-3,4,8-trimethylimidazo[4,5- f]quinoxaline, and 2-amino-1-methyl-6-phenylimidazo[4,5-f]pyridine) were measured by high-performance liquid chromatography. Diets incorporating beef containing low or high levels of HCAs were fed for 12 weeks, during which DMH was administered to induce colon tumors, followed by various dietary regimens as promotional stimuli. Feeding of a beef diet high in HCAs resulted in more DMH-induced colon adenocarcinomas, but only in the context of a low-fat diet. The high-HCA diets increased stomach tumors in all DMH-treated rats. An apparent interaction of high HCA with a high fat level reduced the colon tumor incidence and tumor numbers in those diets containing both factors. These results support the epidemiologic data linking well-cooked meat to increased risk for colon and stomach cancer, but the role of dietary fat level remains puzzling.