Several lines of evidence indicate a role for neuropeptide Y (NPY) in the modulation of the corticotroph axis. In two separate studies reported here, the concentrations of NPY and noradrenaline (NA), as well as corticotropin-releasing factor (CRF) and arginine vasopressin (AVP), were measured in extracts of individual rat hypothalamic nuclei after various manipulations producing either a state of chronic glucocorticoid excess or depletion, and also following repeated restraint stress. Alterations induced in the activity of hypothalamic neurones were inferred from the respective changes in these concentrations. 12 days after bilateral adrenalectomy (ADX), NPY levels were decreased by 24% in the arcuate nucleus (ARC) and 23% in the paraventricular nucleus (PVN, p < 0.05 vs controls). Forced immobilization of the animals for 4 h each day for 9 consecutive days (repeated stress) also decreased NPY content of the ARC by 25% (p < 0.01 vs controls), an effect blocked by the administration of glucocorticoids. NA levels in both hypothalamic nuclei were unaffected by repeated stress or ADX. Administration of glucocorticoids in the first of these studies induced decreases in NA levels by 15% and 25% in the ARC and PVN respectively (p < 0.05 vs controls). However, in subsequent experiments no significant effect of glucocorticoids on NA was observed. Our results demonstrate that the activity of the hypothalamic NPY-ergic neurones is modulated by glucocorticoids and by chronic stress. They also suggest that brainstem catecholaminergic and hypothalamic NPY-ergic neurones are differentially affected by altered glucocorticoid concentrations or by chronic stress, possibly in a stimulus-specific way.