Background. Although colorectal cancer is not one of the major tobacco-related cancers, a possible association with tobacco has been suggested following the observation of a relationship between cigarette smoking and colorectal adenomas. The issue of a long latency of tobacco on colorectal carcinogenesis has also been suggested, since elevated relative risks were observed in long-term smokers. Methods. The association between colorectal cancer and cigarette smoking has been investigated using data from a case-control study conducted in northern Italy between 1985 and 1991 on 955 cases of colon and 629 cases of rectal cancer and 2,879 controls in hospital for acute, nonneoplastic, nondigestive tract, non-tobacco-related diseases. Odds ratios (OR), and the corresponding 95% confidence intervals, of colorectal cancer according to various measures of tobacco smoking were derived from multivariate models, including terms for sex, age, total calorie intake and selected dietary variables, alcohol consumption, and family history of colorectal cancer. Results. No association between smoking and colorectal cancer was observed. Compared with people who had never smoked, the overall multivariate OR for colorectal cancer was 0.9 in ex-smokers and 0.7 in current smokers. No relationship was found with number of cigarettes smoked (OR = 0.7 for both <15 and 15-24, and 0.8 for greater than or equal to 25 cigarettes per day), age at starting (OR = 0.7 for <20, 0.8 for 20-29, and 0.9 for greater than or equal to 30 years), duration (OR = 0.8 for <10, 0.7 for 10-19, 0.8 for 20-29, and 0.7 for greater than or equal to 30 years), and time since starting (OR = 0.7, for <30, 0.8 for greater than or equal to 30 years) and since stopping (OR = 1.1 for <10, 0.7 for greater than or equal to 10 years). There was no evidence of a trend in risk with increasing lifelong pack years (OR for greater than or equal to 40 pack-years = 0.8 for colon and rectum), pack-years before age 30 (OR = 0.7 for greater than or equal to 20 pack-years), or pack-years after age 30 (OR = 0.8 for greater than or equal to 30 pack-years). The results were similar for males and females. Conclusions. The findings of this study indicate that smoking was not a strong risk factor for colorectal cancer, even after a long induction period. (C) 1995 Academic Press, Inc.