Subchronic treatment with the selective serotonergic reuptake inhibitors (SSRIs) fluoxetine, venlafaxine and paroxetine, but not sertraline, were previously shown to specifically impair vigilance performance. The current study was designed to compare the vigilance effects of subchronic treatment with the SSRIs sertraline and citalopram in healthy volunteers, according to a placebo-controlled, double-blind, three-way cross-over design. Twenty-four healthy subjects, aged 30-50 years, of whom 21 completed the study, underwent three treatment periods of 2 weeks in which they received sertraline (50 mg on days 1-8, 100 mg on days 8-15), citalopram (20 mg on days 1-8, 40 mg on days 8-15) and placebo. Treatment periods were separated by 14 days washout periods. Vigilance performance was assessed through a 45-min Mackworth Clock Test at days 1, 8 and 15 of each treatment period. It was found that citalopram impaired vigilance performance acutely after the first 20 mg dose and subchronically after 40 mg daily doses. By contrast, no vigilance impairment was found during sertraline treatment. Sertraline is the only SSRI studied so far with no detrimental effects on vigilance. This may be due to the affinity of sertraline for the dopamine reuptake site. Because citalopram is the most specific SSRI showing this effect, it is concluded that the SSRI-induced decrement of vigilance performance is specifically associated with serotonergic reuptake inhibition.