In morphine-pentobarbital anesthetized dogs (n = 25) we measured the effect of cerebroventricular administration of hypertonic sodium chloride (NaCl) on mean arterial pressure (MAP), heart rate (HR), and integrated renal nerve activity (RNA); in separate experiments (n = 9) we also evaluated the effect of hypertonic NaCl on the osmolarity and electrolyte and catecholamine concentrations of both the blood and the cerebrospinal fluid (CSF); plasma arginine vasopressin (AVP), cortisol, and renin activity were also measured. The intraventricular (ivt) injection of 1.5 M NaCl caused a hypertensive response associated with tachycardia and a significant decrease in RNA (P less than 0.001). Intravenous hexamethonium chloride prevented the changes in HR and RNA, whereas the increases in MAP were markedly reduced but not abolished. The neurohormonal effects of ivt hypertonic NaCl consisted of activation of the sympathoadrenal pituitary axis as reflected by significant increases in the plasma levels of norepinephrine (NE), epinephrine, AVP, and cortisol. On the other hand, there was a significant decrease in plasma renin activity not associated with any significant changes in plasma osmolarity and serum electrolytes. These hormonal changes coincided with an increase in the concentration of CSF NE, CSF Na+, and CSF osmolarity obtained from the cisterna magna. Altogether the results indicate that central administration of hypertonic NaCl in dogs with intact baroreflexes causes a preferential activation of the sympathetic nervous system to vascular systems other than those of the kidneys. In addition, a part of the pressor response may be due to the activation of nonneurogenic mechanisms.