The effects of nitrous oxide at subanesthetic doses (0%, 10%, 20%, and 40% in oxygen) on mood and psychomotor performance were determined in a group of 12 healthy volunteers (six males and six females). A randomized, placebo-controlled, double-blinded, crossover trial of five experimental sessions was used. Effects were measured before, during and after a 30-min inhalation period of the agent, using three subjective effects questionnaires (the Profile of Mood States, the Addiction Research Center Inventory, and the Visual Analogue Scale); and two psychomotor tests (auditory reaction time and Digit Symbol Substitution Test). In addition, an End-of-Session questionnaire, administered 60min after cessation of inhaling the agent, was used, which measured the subjects' reactions to the agent inhaled that day (i.e. peak concentration effect and concentration liking). The primary effects observed from nitrous oxide were confined to the inhalation of 20% and 40% concentrations. Subjects became more confused, sedated, high, dysphoric, and stimulated during inhalation of 40% nitrous oxide; fatigue, depression and anxiety increased after inhalation of 40% nitrous oxide had ceased. Significant or near-significant differences on several measures of subjective effects emerged between sexes. On the End-of-Session questionnaire, subjects' ratings of the peak effect of nitrous oxide were dose-related. There was individual variation in the degree to which subjects liked nitrous oxide: eight of the 12 subjects reported liking the 40% concentration, one was neutral, and three did not like it. Subjects' performance on the DSST was significantly impaired during inhalation of 40% nitrous oxide, but recovered soon after inhalation stopped. In summary, nitrous oxide had robust effects on mood, there appeared to be sex differences in the magnitude of subjective effects of nitrous oxide, and there was some variability in the extent to which subjects liked the anesthetic agent.