There is increasing evidence that peptides in the brain are important in the control of food intake. Administration of opioid and CCK peptides have elicited hunger and satiety, respectively. To evaluate the interaction of these peptides and their role in the central nervous system, concentrations of met-enkephalin were measured in the hypothalamus of rats following peripheral administration of CCK; in addition, effects of feeding and fasting and obesity were studied. In CCK- vs. saline-injected rats met-enkephalin concentrations were decreased in the paraventricular nucleus (PVN), suprachiasmatic nucleus (SC), supraoptic nucleus (SON), dorsomedial hypothalamus (DMH) and ventromedial hypothalamus (VMH). In fed compared with fasted rats met-enkephalin concentrations were higher in the anterior hypothalamus (AH) and lower in the SC; in obese compared with lean rats, concentrations were higher in the AH, PVN, SC, SON, DMH, lateral hypothalamus and VMH. These results show that peripheral injections of CCK can decrease concentrations of met-enkephalin in the brain and suggest a mechanism by which these peptides may interact to influence behavior. In addition, the findings support the hypothesis that the hyperphagia which is typical of obese rats may be due to increased concentrations of met-enkephalin.