The purpose of this study was to characterize the reinforcing, subjective and psychomotor effects of nitrous oxide in healthy volunteers with different alcohol histories. Subjects were divided into two groups: light drinkers (n = 9) and moderate drinkers (n = 10). A choice procedure was used in which subjects first sampled placebo and a given concentration of nitrous oxide, and then chose between the two. Nitrous oxide concentration varied across the four-session experiment from 10-40%. Besides choice, subjective and psychomotor effects served as dependent measures. The majority of subjective effects of nitrous oxide, and its psychomotor-impairing effects, did not vary as a function of drinking group. However, a Wilcoxon rank sum test showed that the median number of times moderate drinkers chose nitrous oxide (three) was significantly higher than the median number of times light drinkers chose nitrous oxide (one). This study provides suggestive evidence that the reinforcing effects of nitrous oxide are modulated by alcohol history.