The effect of norepinephrine (NE) injection (40 nmol) into the paraventricular nucleus (PVN) on plasma insulin and glucose levels was studied in freely moving lean Zucker rats bearing chronic right jugular catheters for blood sampling and unilateral intracerebral cannulas placed just above the PVN. Already 2.5 min after NE injection, plasma glucose levels rose significantly, reaching a peak at 10 min poststimulus, whereas the insulin output was strongly inhibited. This NE-induced hyperglycemia was independent of the corticosterone levels. A ganglionic blockade performed by intravenous chlorisondamine (1 mg/kg body wt) reduced by 80% the 4.5-min NE-induced incremental glucose areas. NE-induced hyperglycemia was reduced to a large extent when the PVN alpha-adrenergic receptors were blocked with phentolamine and to a lesser extent when the beta-adrenergic receptors were blocked with propranolol. NE-induced inhibition of insulin output was not affected by these adrenergic blockers. It is concluded that, when administered locally into the PVN, NE can activate the sympathetic outflow expressed by a neurally mediated hyperglycemia through central alpha- and beta-adrenoreceptor and an inhibition of insulin output through other types of receptors and/or mechanisms.