To evaluate the oα-noradrenergic regulation of arginine vasopressin (AVP) and oxytocin (OT) in normal humans, we measured the effect of the α2-agonist clonidine on concentrations of these neuropeptides in both plasma and cerebrospinal fluid (CSF). Subjects underwent two lumbar puncture studies, one of which was performed 100 min after oral administration of 5 µg/kg clonidine. Plasma AVP and OT were measured at a single time point 10 min before lumbar puncture. Both plasma and CSF AVP were significantly lower in the clonidine condition than in the control (no drug) condition. Neither plasma nor CSF OT differed significantly between conditions. Our data confirm previous reports of α2-noradrenergic inhibition of neurohypophyseal release of AVP into blood, and extend these findings to healthy human subjects. Our data also suggest that AVP appearance in CSF, presumably from extraneurohypophyseal vasopressinergic neurons, is regulated by an inhibitory oα-noradrenergic mecha