Despite numerous studies which have characterized the regulation of antidiuretic hormone (ADH), the role of volume in governing ADH release remains incompletely defined. Most studies have examined the quantitative effects of hypovolemia on arginine vasopressin (AVP). In contrast, few have assessed the role of hypervolemia on AVP regulation. Furthermore, there are no data to date on the effect of acute isoosmotic volume expansion on plasma AVP in man. The successful characterization of the water immersion model (NI) and the demonstration that it induces an acute central volume expansion without changes in plasma composition commended its utilization in the present study. Twelve normal subjects were studied after 14 h of dehydration on two occasions: control and during 4 h of NI. Blood was obtained every 30 min for AVP. AVP was unaltered during the control period. In contrast, there was a prompt and sustained suppression of AVP throughout NI (P < 0.05 vs. control). There were no concomitant changes in plasma osmolality. Since the changes in AVP occurred consequent to central volume expansion but in the absence of concomitant changes in plasma composition, the current data support the concept that acute isoosmotic central volume expansion in man results in a suppression of plasma AVP.