Both beta-endorphin and clonidine proved to have statistically significant analgesic activity (increase in latency to hind-paw lick in hot plate test) in rats. Furthermore, the pain inhibition induced by beta-endorphin and clonidine could be antagonized by prior treatment of animals with either naloxone (a narcotic antagonist) or the depletors of central serotonin pathways such as 5,6-dihydroxytryptamine, 5,7-dihydroxytryptamine and p-chlorophenylalanine have not effect on latency to hind-paw lick. The data indicate that serotoninergic activity in the brain plays a role in the elaboration or modulation of beta-endorphin and clonidine analgesia in rats.