The effects of intrahypothalamic administration of norfenfluramine (NFFL), an anorectic agent that increases serotonergic transmission, on plasma concentrations of glucose, free fatty acids (FFA), and their regulating hormones were investigated in resting and exercising rats. Infusion of 5 micrograms NFFL in 0.125 microliter aCSF/min into the nucleus paraventricularis of the hypothalamus (PVN) caused a significant increase of blood glucose, plasma epinephrine (E), and corticosterone concentrations. Plasma levels of FFA, insulin, or norepinephrine (NE) remained unchanged. Lower doses of NFFL (0.5 and 0.05 microgram/min) did not affect peripheral metabolism. The effects of NFFL in the PVN were completely prevented by prior administration of a 5-HT1 antagonist, (S)-(-)propranolol. The exercise-induced increase of plasma NE was reduced after prior administration of 5 micrograms NFFL/min into the PVN. Plasma E responses tended to be increased. The exercise-induced alterations in glucose, FFA, corticosterone, and insulin were not affected by NFFL infusion into the PVN. The data suggest that activation of serotonergic mechanisms in the PVN might change the neurohormonal response to a stressor favouring the release of adrenal hormones above activation of the neuronal branch of the sympathetic nervous system.