We recently demonstrated in patients with panic disorder that hypertonic saline infusion induces acute panic with the same frequency and intensity as the standard hypertonic sodium lactate infusion. We now report the effects in normal men of hypertonic saline infusion on neuroendocrine systems possibly relevant to panic and anxiety. We administered a 150-min infusion of hypertonic saline (5% sodium chloride) which increased plasma osmolality from 288 +/- 1 to 303 +/- 2 mOsm/kg and produced the appropriate increase of plasma arginine vasopressin (AVP). Plasma norepinephrine (NE) increased substantially during hypertonic saline infusion compared to a normal saline infusion of equal volume and duration. Mean arterial pressure (MAP) also increased and there were significant positive correlations between MAP and NE, but not between MAP and AVP during hypertonic saline infusion. Plasma epinephrine and cortisol did not differ between conditions. Although the pattern of plasma adrenocorticotrophic hormone (ACTH) response differed between hypertonic saline and normal saline conditions, ACTH concentrations did not increase compared to baseline in either condition. These data suggest that hypertonic saline infusion increases sympathetic nervous system activity in normal men.