Individuals who are fast NAT2 acetylators may be at increased risk of colorectal cancer through the activation of carcinogenic heterocyclic amines, which are produced by meat cooked at high temperatures and are found in cigarette smoke. To investigate this hypothesis a study of 500 incident colorectal cancer cases and population controls, matched for age, sex and general practitioner, was conducted in the United Kingdom. Usual meat intake and lifetime smoking habits were estimated using a detailed food frequency questionnaire administered by interview. Subjects indicated how well cooked they ate their meat by responding to verbal or picture prompts. Subjects were classified as fast or slow NAT2 acetylators on the basis of NAT2 genotype using previously described phenotype-genotype correlations. Complete data were available on 433 matched pairs. The risk of colorectal cancer showed a steady increase with meat intake, rising to an odds ratio of 1.68 (95% confidence interval (1.11, 2.54)) for the highest versus the lowest quartile, and this was even more pronounced for red meat (odds ratio 2.33 (1.56, 3.48)). However this effect was not influenced by the preference for well-done meat. Smoking was also associated with an increased risk (odds ratio 1.47 (1.10, 1.98) for ever- versus never-smokers). In both cases and controls approximately 40% of subjects were classified as fast acetylators, and the risks associated with (red) meat intake and smoking did not vary according to NAT2 phenotype. This study provides no support for the hypothesis that fast NAT2 acetylators are at increased risk of colorectal cancer, even if exposed to high levels of heterocyclic amines from well-cooked meat or smoking. The effect of meat, which has been observed previously, could be due to fat content or to other correlates of high meat consumption in diet or lifestyle.