To assess dynamically a seasonal variation in the functioning of the central serotonin (5-HT) system, we investigated the prolactin (PRL) response to the specific serotonergic agent D-fenfluramine (D-FEN) in the different seasons of the year. Thirteen healthy women and 11 healthy men (six for each season), aged 20-50 years, received PO 30 mg D-FEN and placebo, according to a randomized double-blind design. As compared to placebo, D-FEN induced a clear-cut increase in plasma PRL levels in all the seasons; this response was higher in fall than in spring and summer (p < .01 and < .05, respectively). In all the subjects, as a group, the hormone response to the 5-HT probe was inversely correlated with the body weight and age. These results document a seasonal variability in the PRL response to D-FEN, which suggests a seasonal fluctuation in central 5-HT transmission in healthy humans.