Our presently somewhat limited knowledge of the modulation of the content, release and turnover of endorphins in brain and pituitary by acute and chronic drug treatment is reviewed and discussed particularly in relation to the problem of addiction. In vitro studies in striatal slices and isolated anterior and intermediate/posterior lobes of the pituitary point to the existence of specific interactions between endorphins and neurotransmitters. In vivo studies have revealed acute GABA-mediated effects of benzodiazepines upon striatal levels of met-enkephalin activity. Morphine exerts no acute effects upon endorphin levels, but decreases the levels of particular endorphins in specific areas of brain and pituitary after long-term treatment; somewhat similar effects are observed after prolonged intake of ethanol, whereas chronic haloperidol treatment results in an increase in levels of endorphins in brain and pituitary. Incorporation studies employing the intermediate/posterior lobe of the pituitary have revealed that the changes in beta-endorphin levels produced by prolonged treatment with morphine or haloperidol reflect a respective depressed or enhanced synthesis of the beta-endorphin precursor pro-opiocortin, whilst the enzymatic processing of this precursor remains unmodified. Studies in cell-free preparations demonstrated that m-RNA extracted from the intermediate/posterior lobes of chronically morphinized rats possesses a decreased "activity".