Microdialysis was used to monitor serotonin, 5-hydroxyindoleacetic acid (5-HIAA) and the metabolites of dopamine, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the perifornical lateral hypothalamus (PFH) of freely moving rats. Systemically administered d-fenfluramine (d-FEN) increased extracellular serotonin, DOPAC and HVA, while decreasing serotonin's metabolite 5-HIAA. Local application of d-FEN directly to the hypothalamic terminal region caused large increases in extracellular serotonin and had a tendency to decrease all 3 metabolites. This effect was confirmed when d-FEN was infused locally by reverse dialysis. These results provide direct evidence that the anorectic drug d-FEN can increase extracellular serotonin in the hypothalamus in vivo and suggest a serotonergic action in the perifornical region. This finding is consistent with our report that a meal also increases serotonin in this region.