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 re-analysis of alcohol challenge data on 412 Australian twins was performed 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 self-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 model-fitting 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.