Serotonergic mechanisms mediate the expression of personality traits linked to vulnerability to psychological illness such as impulsivity, aggression and anxiety; and modulate the identification of emotional expressions in the face as well as emotional learning about broader classes of appetitive and aversive signals. Faces with neutral expressions signal a variety of socially-relevant information, such that inferences about the big-five personality traits, including Neuroticism, Extraversion, and Agreeableness, can be accurately made on the basis of emotionally neutral facial photographs. Given the close link between Neuroticism and psychological distress, anxiety and depression, we investigated the effects of diminished central serotonin activity (achieved by tryptophan depletion) upon the accuracy of 52 healthy (non-clinical) adults' discriminations of personality from facial characteristics. All participants were able to discriminate reliably four of the big-five traits, including Neuroticism. However, the tryptophan-depleted participants were specifically less accurate in discriminating Neuroticism than the matched non-depleted participants. These data suggest that central serotonin activity modulates the identification of, not only negative facial emotional expression, but a broader class of signals about personality characteristics linked to psychological distress.