Although diet and its constituents have been studied extensively as risk factors for colon cancer, much less is known about how specific types of fluid influence colon cancer risk. In this study, we explored associations between colon cancer and total fluids, water and methylxanthine-containing beverages such as coffee, tea and cola; data were obtained from 1,993 incident cases of colon cancer and 2,410 population-based controls living in California, Utah and Minnesota. Our primary objective was to determine the influence on associations of amount consumed, confounding and effect modification. We observed few important differences between colon cancer and fluid consumption for all subjects combined. Among men, low levels of coffee intake were associated with an increased risk of colon cancer relative to non-consumers of coffee (OR 1.32, 95% CI 1.02-1.67), while at high levels of consumption, an inverse association was observed (OR 0.81, 95% CI 0.58-1.12). The observed associations were only slightly influenced by consumption of water or other potential confounding factors, but changing the referent group to those consuming one cup of coffee per day or less resulted in a stronger association and a more significant inverse linear trend (OR 0.71, 95% CI 0.53-0.96). The associations with coffee and caffeine- and methylxanthine-containing beverages were strongest for proximal tumors in men. High levels of water intake, however, were protective for distal tumors (OR for men 0.68, 95% CI 0.49-0.96). Assessment of the impact of smoking on associations between colon cancer and coffee showed a significant interaction between smoking and coffee for both men and women.