Many studies have found genetic effects to contribute to alcoholism risk in both men and women. Based on preliminary evidence for shared genetic risk between smoking and drinking problems, a reanalysis of alcohol challenge data on 412 AustraUan twins was perfonned to explore the possibility that smoking may diminish or moderate the intoxicating effects of alcohol. We found history of smoking to be strongly associated with seIf-reported intoxication after alcohol challenge in women (women: r = -0.44 ± 0.08; men: r = -0.21 ± 0.08), comparable with self-reported average weekly consumption of alcohol, which was more strongly associated in men (women: r = -0.37 ± 0.07; men: r = -0.54 ± 0.06). Structural equation modelfitting indicated a strong association between heavy drinking and smoking, but the association between smoking and postalcohol intoxication remained even when the effects of heavy drinking were controlled for. These results prompt the question of whether smoking cigarettes directly influences the transition from moderate to excessive use of alcohol by diminishing feelings of alcohol intoxication.Key Words: Alcohol Intoxication, Alcohol Challenge, SmOking.F INDINGS FROM twin and adoption studies are consistent with an important genetic contribution to alcoholism risk in men, and at least some studies suggest a genetic influence on alcoholism in women (reviewed in refs. 1 and 2). A relationship between smoking tobacco and the excessive use of alcohol has been recognized for many years. 3 Recently, a population-based study found those who have ever smoked to have five times the risk of developing alcoholism as compared with nonsmokers. 4 A series of twin studies of smoking behavior yielded results in both men and women consistent with an important genetic influence on various aspects of smoking: whether or not an individual becomes a smoker, how much she or he smokes, and whether or not he or she quits successfully or becomes a persistent long-term smoker.5-12 It is therefore natural to