To study the role of hot mate drinking, alcohol, tobacco, and diet in esophageal cancer, a case-control study including 131 cases and 262 hospital controls was carried out in La Plata, Argentina. In multivariate analyses, statistically significant increases in risk were detected for alcohol, tobacco, and some dietary factors but not for hot mate drinking. A strong dose-response relationship was observed with the amount of alcohol consumed daily but not with the number of cigarettes smoked. The odds ratio for those drinking more than 200 ml of ethanol/day compared to nondrinkers was 5.7 (95% confidence interval, 2.2-15.2). An increased risk was also observed for those eating barbecued meat more than once a week (odds ratio, 2.4; 95% confidence interval, 1.2-4.8) as compared to those eating it less than once a week, and a reduction in risk was associated with daily consumption of nonbarbecued beef as compared to those eating it less than daily. Concerning mate drinking, the only variable that showed an effect was the temperature at which mate is drunk. Those who reported drinking mate hot or very hot as compared to those drinking it warm had an increase in risk (odds ratio, 1.7; 95% confidence interval, 1.0-2.9). Our findings strengthen the evidence for an important role of alcohol and tobacco in esophageal carcinogenesis but do not provide strong support for a role of hot mate drinking.