Male Sprague-Dawley rats were fed a high calorie, high fat diet for 3 months to produce chronic diet-induced obesity (DIO) in which they gained 70% more weight than chow-fed controls. Thirty-six percent of the rats fed the DIO diet resisted the development of obesity (DR), gaining no more weight than chow-fed controls but serving as a comparison for the effects of the diet alone on the metabolism of brain catecholamines. The major influence of dietary composition was upon norepinephrine (NE) metabolism. Both DIO and DR rats had increased turnover of NE (107-217%) and/or shorter NE half-lives (42-67%) than controls in the hypothalamic paraventricular (PVN) and dorsomedial (DMN) nuclei and the median eminence (ME); dopamine (DA) turnover was similarly accelerated in the PVN. The DR rats alone exhibited decreased NE levels with increased disappearance of NE in frontal cortex and increased disappearance of DA in the ventromedial hypothalamic nucleus (VMH). The major effect of chronic obesity alone was a 31-33% decrease in DMN DA turnover and an 80% decrement in ME DA turnover associated with a 61% decrease in DA levels as compared to chow-fed controls. Therefore, the major effect of a high calorie, high fat diet was a diffuse acceleration of brain NE and DA turnover while chronic obesity led to decreased DA turnover in the DMN and ME.