The often observed association between red meat and colorectal cancer could be due in part to mutagens, such as heterocyclic amines (HCA), that are present in cooked meat. HCAs are highly mutagenic and cause intestinal tumors in animals. The hypothesis that HCAs are also carcinogenic to humans remains to be substantiated in epidemiologic studies. We determined the associations of meat preparation and frequency of intake (proxy variables for HCA exposure, since HCA concentration depends on the type of meat and the way it is cooked) with the prevalence of distal colorectal adenomas in a sigmoidoscopy-based case-control study of 488 matched pairs of subjects from two California (United States) Kaiser Permanente Medical Centers. A more than twofold difference in adenoma prevalence between subjects at extreme ends of estimated HCA intake was observed. For subjects who ate red meat more than once per week, fried it more than 10 percent of the time, and ate it with a darkly browned surface, compared with subjects who ate red meat one time or less per week, fried it 10 or less percent of the time, and ate it with a lightly browned surface, the odds ratio was 2.2 (95 percent confidence interval = 1.1-4.3). Adenoma prevalence also increased with frequency of frying red meat (P trend = 0.004). These results are consistent with a carcinogenic effect of HCA.