Serotonin constrains a broad array of animal and human behavior and may also inhibit the expression of mood or affective states among humans. For the most part, this research has focused on the association of central serotonergic function with negative affectivity (i.e., anxiety, depression, hostility), with less attention on the relationship between serotonergic function and positive affect or mood. The current study was conducted to examine the relationship between a measure of central serotonergic activity and daily ratings of positive and negative mood in a nonpatient sample. Two hundred and fifty-four adults, aged 24-60, completed end-of-day ratings of positive and negative mood items over 7 consecutive days. A neuropharmacological challenge was administered to index central serotonergic function, i.e., the maximal prolactin (PRL) response to fenfluramine, a serotonin releasing agent. Hierarchical linear regression analyses indicated that the peak PRL response to fenfluramine was positively associated with positive mood, averaged over 7 days, after controlling for known predictors of the PRL response. This relationship remained significant after controlling for average negative mood, for the presence of a current DSM-III-R diagnosis, and for trait measures of Neuroticism and Extraversion. In contrast, the PRL response to fenfluramine was not associated with average negative mood, although it was inversely correlated with trait negative affectivity (i.e., Neuroticism). These results suggest that deficiencies in serotonergic function may reflect the relative absence of positive mood.