We posed the question whether the cognitive enhancement caused by nicotine in human subjects is mediated by dopamine (DA) release. This issue was addressed by testing performance in the Wesnes and Warburton vigilance task after s.c. nicotine with or without concomitant oral haloperidol. The subjects were moderate (10-14 cigarettes/day) smokers after overnight deprivation of smoking. After an initial practice session, each subject participated in four further sessions spread over 2 weeks, after: placebo/placebo, placebo/haloperidol (5 mg), placebo/nicotine (0.8 mg) or nicotine/haloperidol, double-blind with a balanced ordering of drug combinations. On each occasion, performance was measured on the vigilance task, a finger tapping test, and digit span forward and backward. Nicotine improved detection sensitivity on the vigilance task, and this effect was unchanged by haloperidol; the latter compound reduced forward digit span. Thus, the improved vigilance caused by nicotine does not appear to be mediated by DA systems.