Ethanol and nitrous oxide (N2O) are sometimes used in combination by recreational drug users. The subjective effects of this drug combination have not been examined, and was the basis for the present study. The effects of both drugs were examined alone and in combination. Dependent measures included mood, cognitive/psychomotor performance, and pain reports. Volunteers (N = 11) first consumed a drink containing ethanol (0, 0.25, or 0.5 g/kg), waited for 15 min, and then inhaled 100% oxygen (placebo) or 30% N2O in oxygen for 35 min. Thirty minutes into the inhalation, subjects immersed their non-dominant forearm in icy water for 3 min. Ethanol increased ratings of 'feel drug effect' and 'drunk'. N2O affected several mood ratings, impaired cognitive/psychomotor performance, and reduced pain reports. There were several instances of ethanol potentiating the effects of N2O, and instances in which the drug combination produced effects that neither drug alone did. Ethanol did not potentiate the analgesic effects of N2O. Overall, the data obtained in the study did not convincingly demonstrate that the drug combination of N2O and ethanol had a greater abuse liability than did N2O alone, at the doses that were tested.