The associations between colorectal cancer risk and several chronic illnesses, operations, and various medications were examined in 715 colorectal cancer cases and 727 age/sex-matched controls in data derived from a large, comprehensive, population-based study of this cancer conducted in Melbourne, Australia. There was a statistically significant deficit among cases of hypertension, heart disease, stroke, chronic chest disease, and chronic arthritis and a statistically significant excess of “hemorrhoids” among cases, and all of these differences were consistent for both colon and rectal cancer and for both males and females. Although no statistically significant differences were found for other cancers, there were twice as many breast cancers among cases (16) than among controls (8) and also there were 9 uterine cancers among cases and only 2 among controls. There was a statistically significant deficit among cases in the use of aspirin-containing medication and vitamin supplements, and this was consistent for both colon and rectal cancer and for both males and females. There was a statistically significant excess of large bowel polypectomy among cases. The modeling of these significant associations simultaneously in a logistic regression equation indicated that hypertension, heart disease, chronic arthritis, and aspirin use were each independent effects and consistent for both colon and rectal cancer for both males and females and also that these effects were independent of dietary risk factors previously described in the Melbourne study. The possible relevance of these findings towards an understanding of colorectal cancer risk and etiology is discussed.