To provide further insight on the relationship between macronutrients and colorectal cancer, overall and by specific subsite(s), we carried out between 1992 and 1996 in 6 Italian areas a case-control study on 1,953 individuals of both sexes with incident colorectal cancer (age range 19-74) and 4,154 controls (age range 19-74) in hospital with acute, non-neoplastic diseases. A validated food-frequency questionnaire was used, including questions on 78 foods or recipes and on individual fat-intake pattern. The risk of cancer of the colon and rectum increased with total energy intake (odds ratio in highest vs. lowest quintile 1.43 and 1.50, respectively). The risk also rose significantly with an increase of starch intake, whereas it moderately decreased with an increase of protein intake. Monounsaturated fat intake appeared uninfluential, while saturated fat intake showed a modest direct association with rectal cancer. Polyunsaturated fat intake was inversely associated with colon cancer risk, particularly with the right colon.