Dogs were prepared for experiments by chronic implantation of catheters into the hepatic portal vein. Intraportal infusions of hypertonic saline, 5 ml/min, increased plasma antidiuretic hormones (rat bioassay) in absence of significant changes in systemic plasma osmolality. In the 5th min of 1.8, 2.7, or 3.6% saline infusion, plasma antidiuretic hormone (ADH) increased significantly from 3.2 +/- 0.7 to 14.3 +/- 3.6 (SE) microU/ml, from 2.3 +/- 0.4 to 42.0 +/- 7.6 microU/ml, and from 1.9 +/- 0.6 to 64.4 +/- 16.8 microU/ml, respectively. In control experiments plasma ADH did not change with isotonic saline infused intraportally or with 3.6% saline given into a systemic vein. The transsection of hepatic vagal afferent fibers abolished plasma ADH increase dependent on hypertonic intraportal infusion. The data support the existence of osmoreceptors within the portal vascular bed and indicate ADH involvement in the control of fluid balance by intrahepatic blood osmalality. The information on osmolality changes is neurally transmitted to the hypothalamus via hepatic vagal afferents. A demonstration of an increase in portal but not systemic blood osmolality following food intake suggests that intrahepatic osmoreception may be important in physiological regulation of water metabolism.