To investigate the role of tobacco and alcohol use and dietary factors in the etiology of small intestinal adenocarcinoma, we analyzed data from a large population-based case-control study of multi-site cancers conducted in Los Angeles County between 1975 and 1984. The present analysis included interview information on 36 small intestinal adenocarcinoma patients and 998 population controls. After adjusting for age and ethnicity, men who smoked more than 100 cigarettes during their lifetimes were at a non-significantly 3-fold increased risk for small intestinal adenocarcinoma; this association was substantially weaker in women. In men and women combined, a significant 3-fold increased risk in heavy drinkers (80+ g ethanol/day) relative to more moderate drinkers and non-drinkers was observed. Although frequent (>6 times vs. less than 2 times of intake a week) intake of foods rich in heterocyclic aromatic amines (based on the combined intake of fried bacon and ham, barbecued and/or smoked meat and smoked fish) was associated with a significant 4.5-fold increased risk of small intestinal adenocarcinoma in men; this association was not present in women. Based on 2 questions that provided a crude assessment of sugar intake, risk of small intestinal adenocarcinoma in men and women appeared to be associated with adding sugar regularly in coffee or tea and daily intake of non-diet carbonated soft drinks. When we computed total sugar intake from tea, coffee and non-diet carbonated soft drinks, there was a consistent and significant trend of increasing sugar intake and risk of small intestinal adenocarcinomas. Compared with the lowest intake level a day (<5 g), medium (5-25 g) and high intakes (>25 g) were associated with ORs of 2.5 and 3.8, respectively.