Osmoregulation of vasopressin release was studied in 15 quadriplegic subjects (Quad) and 7 healthy control subjects (Con). Hypertonic NaCl (0.85 M) was infused intravenously (0.05 ml.kg-1.min-1) over 90 min in studies on supine subjects and in comparable studies on the same subjects erect (sitting). Erect posture in Quad, but not in Con, was accompanied by orthostatic reductions in arterial blood pressure and by significantly increased plasma aldosterone (P less than 0.001) and cortisol (P less than 0.001) concentrations and increased plasma renin activity (P less than 0.025). Changes in plasma arginine vasopressin concentration (PAVP) during hypertonic NaCl infusions were also greater in erect than in supine Quad (P less than 0.005), despite identical changes in plasma osmolality (Posm). Linear regression analysis of the PAVP/Posm relationship during hypertonic NaCl infusions showed highly significant correlations (P less than 0.0002) in both Quad and Con. Mean slope values for regression lines, however, were significantly higher in erect than in supine Quad (P less than 0.005) but did not differ in relation to posture in Con. Differences in posture were not associated with differences in abscissal intercepts in either Quad or Con. These studies show significant alterations in the sensitivity of osmotically stimulated vasopressin release related to differences in posture in Quad, characterized by enhanced sensitivity in erect posture due to nonosmotic stimuli not evident in Con.