Hindbrain norepinephrine (NE) and epinephrine (E) neurons play a pivotal role in the central distribution of sensory signals derived from the internal environment. Their projections influence the various secretory patterns of the hypothalamo-pituitary-adrenal axis and are essential for feeding and adrenal medullary responses to glucoprivation. NE and E terminals in the paraventricular nucleus of the hypothalamus (PVH) and associated hindbrain cell bodies can be virtually eliminated by PVH microinjection of a retrogradely transported conjugate of saporin (SAP, a ribosomal toxin) and a monoclonal antibody against dopamine beta-hydroxylase (dbetah), i.e. dbetah mouse monoclonal antibody conjugated to SAP (DSAP). To examine the effects of selective elimination of NE/E afferents on hypothalamo-pituitary-adrenal activation, we injected DSAP into the PVH and measured corticosterone secretion under basal circadian conditions and in response to two distinct challenges: glucoprivation and forced swim. DSAP lesions profoundly impaired glucoprivation-induced corticosterone secretion and induction of CRH heteronuclear RNA and Fos mRNA in the PVH, without impairing basal CRH mRNA expression, circadian corticosterone release, or the corticosterone response to swim stress. Thus, NE/E projections influence corticosterone secretion only in certain circumstances. They are required for the response to glucoprivation, but are dispensable for circadian activation and for the response to swim stress.