The serotonergic modulation of the brain, pituitary and gut beta-endorphin and dynorphin systems in the rat was determined pharmacologically. Acute administration of fenfluramine (20 mg/kg), m-chlorophenylpiperazine (m-CPP 2.5 mg/kg), fluvoxamine (15 mg/kg) and 5-hydroxytryptophan (5-HTP 160 mg/kg) increased immunoreactive (ir)beta-endorphin (beta E) in the hypothalamus and decreased it in the anterior lobe of the pituitary. That effect was antagonized by cyproheptadine (1 mg/kg). None of the treatments altered significantly ir-dynorphin (DYN) level in the hypothalamus and pituitary, however, ir-DYN in the gut was dramatically decreased after fenfluramine, m-CPP, fluvoxamine, femoxetine and 5-HTP, the latter effects being antagonized by cyproheptadine. The obtained results suggest that the serotonin system might stimulate the release of the anterior pituitary beta-endorphin and gut dynorphin pools, while the brain beta-endorphin system appears to be inhibited by activation of serotonin neurons.