Little information is available about how fluid intake from beverages and sources of fluid intake influence risk of rectal cancer. We examined these associations with risk of incident rectal cancer in a population-based case-control study of 952 cases and 1,205 controls living in northern California and Utah. We also determined if intake of fiber (soluble and insoluble), physical activity, and nonsteroidal anti-inflammatory medications (NSAIDs) or aspirin modified the associations between fluid intake and rectal cancer. We identified a modest inverse association of water intake (odds ratio, OR = 0.70; 95% confidence interval, CI = 0.48, 1.02) and total fluid intake (high vs. low OR = 0.70; 95% CI = 0.46, 1.06) with risk of rectal cancer in men and a positive association with juice among women (high vs. low OR = 1.56; 95% CI = 1.00, 2.41). Risk of rectal cancer increased nonsignificantly among men with beer consumption, among women with high white wine use, and among men and women with high long-term alcohol use. NSAIDs modified the association of alcohol consumption with rectal cancer: 1) risk associated with beer increased among men who did not take NSAIDs and had a high beer intake (OR = 1.60; 95% CI = 1.08, 2.39) and 2) risk associated with long-term alcohol intake increased in a linear fashion in women who did not use NSAIDs (OR = 1.98; 95% CI = 1.15, 3.40). Risk of rectal cancer increased among estrogen-negative women if they consumed any beer or white wine but decreased among estrogen-positive women with beer. In men, low intake of water and low insoluble fiber intake were associated with increased risk of rectal cancer beyond that of either factor alone (OR = 1.82; 95% CI = 1.11, 3.00). The interactions of fiber with water intake suggest that bowel motility may be the mechanism responsible for modification of rectal cancer risk for water. Associations of alcohol to risk for rectal cancer may be related to cellular hyperproliferation and may be modified by NSAID use.