Hypertonic (2 ml, 598 mosmol/kgH2O) solutions were infused over 4 min via a stomach tube in 12 groups (n = 5-10) of conscious rats with indwelling arterial catheters. Mean changes over 4-21 min of plasma arginine vasopressin (AVP) were 6.1 +/- 0.9 for NaCl (P less than 0.01), 9.3 +/- 3.0 for LiCl (P less than 0.01), 4.5 +/- 1.3 for sodium isethionate (P less than 0.01), 2.8 +/- 0.9 for sucrose (P less than 0.025), 3.9 +/- 2.8 for mannitol (P less than 0.01), and -0.1 +/- 0.1 (SE) pg/ml for urea. The AVP responses to NaCl and sucrose were proportional to the rate of gastrointestinal absorption of radiolabeled NaCl and sucrose, respectively. The AVP response to 598 mosmol/kgH2O NaCl was attenuated by 60.6% (P less than 0.001) in rats with lesion of the side branches of the major splanchnic nerves innervating the mesentery of the upper small intestine and the portal vein area, by 34-37% (P less than 0.05) in rats with right or left splanchnic nerve lesions, and was not affected by subdiaphragmatic vagotomy. Changes in systemic plasma osmolality were small and could not explain the AVP responses. Thus splanchnic receptors are osmosensitive, are situated in the mesentery of the upper small intestine and possibly the portal vein area, and project to the spinal cord via the right and left major splanchnic nerves.