Neuropeptide Y (NPY) is a powerful stimulus to food intake in the rat. Exogenous NPY given into the third ventricle or into the paraventricular nucleus (PVN) of the hypothalamus stimulates both food consumption as well as the hypothalamus-pituitary-adrenal (HPA) axis. Presumably NPY activates the adrenocortical system through direct stimulation of CRF containing cells in the PVN. Food intake is also a major regulator of adrenocortical activation. Rhythms in HPA axis activity follow rhythms in food consumption, and rats that have been food deprived overnight have inhibited HPA axis responses to restraint stress and corticosteroid feedback the following morning. To investigate the interaction of NPY with both feeding and HPA axis activation three sets of experiments were performed: Animals fed ad lib were injected icv with NPY (2.5 micrograms) and allowed access to food or not post injection; animals were fasted overnight prior to NPY injection; finally, dose response experiments were performed to examine the relative sensitivities of feeding and HPA axis activation to exogenous NPY. Ad lib fed animals allowed access to food after NPY injection had slightly greater ACTH responses to NPY while glucocorticoid and insulin responses were not significantly different from ad lib fed animals not allowed access to food post injection. Animals allowed to eat post injection had significantly decreased food consumption the night following injection, however, total 24 h food consumption was not different between these animals and those given food 8 h post NPY injection. In overnight fasted animals NPY injections produced ACTH responses of equal magnitude to those in ad lib fed animals.(ABSTRACT TRUNCATED AT 250 WORDS)