Background. The rates of colon cancer in various countries are strongly correlated with the per capita consumption of red meat and animal fat and, to a lesser degree, inversely associated with the consumption of fiber. Methods. We conducted a prospective study among 88,751 women 34 to 59 years old and without a history of cancer, inflammatory bowel disease, or familial polyposis who completed a dietary questionnaire in 1980. By 1986, during 512,488 person-years of follow-up, 150 incident cases of colon cancer had been documented. Results. After adjustment for total energy intake, animal fat was positively associated with the risk of colon cancer (P for trend = 0.01); the relative risk for the highest as compared with the lowest quintile was 1.89 (95 percent confidence interval, 1.13 to 3.15). No association was found for vegetable fat. The relative risk of colon cancer in women who ate beef, pork, or lamb as a main dish every day was 2.49 (95 percent confidence interval, 1.24 to 5.03), as compared with those reporting consumption less than once a month. Processed meats and liver were also significantly associated with increased risk, whereas fish and chicken without skin were related to decreased risk. The ratio of the intake of red meat to the intake of chicken and fish was particularly strongly associated with an increased incidence of colon cancer (P for trend = 0.0005); the relative risk for women in the highest quintile of this ratio as compared with those in the lowest quintile was 2.49 (95 percent confidence interval, 1.50 to 4.13). A low intake of fiber from fruits appeared to contribute to the risk of colon cancer, but this relation was not statistically independent of meat intake. Conclusions. These prospective data provide evidence for the hypothesis that a high intake of animal fat increases the risk of colon cancer, and they support existing recommendations to substitute fish and chicken for meats high in fat. (N Engl J Med 1990; 323:1664–72.).