The authors examined the association between colon cancer and meat intake categorized by level of doneness, cooking method, and estimated levels of heterocyclic amines (HCAs), benzo[a]pyrene, and mutagenicity. Data were collected as part of a population-based, case-control study of colon cancer in North Carolina between 1996 and 2000 that included 701 African-American (274 cases, 427 controls) and 957 White (346 cases, 611 controls) participants. Odds ratios were calculated by using unconditional logistic regression, comparing the fifth to the first quintile levels of intake or exposure. Intake of red meat was positively associated with colon cancer (odds ratio (OR) = 2.0, 95% confidence interval (CI): 1.3, 3.2). Associations with meat intake by cooking method were strongest for pan-fried red meat (OR = 2.0, 95% CI: 1.4, 3.0). Associations with meat intake by doneness were strongest for well-/very well done red meat (OR = 1.7, 95% CI: 1.2, 2.5). The strongest association for individual HCAs was reported for 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) across all levels of exposure, with odds ratios of 1.8-2.0. Overall, sophisticated exposure measures were used to report modest, positive associations between red meat intake and colon cancer consistent with the hypothesis that HCAs may be among the etiologically relevant compounds in red meat.