The effects of the neurotransmitter serotonin (5-HT) and the neuropeptide cholecystokinin (CCK) on food intake are well established. Based on pharmacological studies, an interactive model for 5-HT and CCK was proposed. The present microdialysis study was aimed to provide neurochemical evidence for a facilitatory effect of CCK-8S on 5-HT release in the lateral hypothalamus under in vivo conditions. The results indicate an increase of extracellular hypothalamic 5-HT both during food intake in previously food-deprived rats and also after systemic administration of 8 microg/kg and 40 microg/kg CCK-8s in food-deprived rats. The results show that peripherally administered CCK-8s induces central serotonergic effects, possibly related to feeding.