OBJECTIVE To examine the osmotic and non-osmotic regulation of thirst and AVP release in patients with compulsive water drinking. METHODS A 2-hour intravenous infusion of hypertonic (855 mmol/l) sodium chloride solution, followed by a 2-hour drinking period. METHODS Seven patients with compulsive water drinking, seven patients with diabetes insipidus and seven healthy controls. METHODS Plasma AVP, osmolality, sodium and haematocrit, thirst ratings on a visual analogue scale and the volume of water drunk in 2 hours following infusion. RESULTS Plasma AVP responses to osmotic stimulation, and non-osmotic inhibition by drinking, were normal in patients with compulsive water drinking. Basal thirst ratings were higher in compulsive water drinking than in either diabetes (P less than 0.001) or controls (P less than 0.001), despite lower basal plasma osmolalities. There was a significant rise in thirst ratings during saline infusion, which correlated closely with plasma osmolality, in all three groups, but the final thirst ratings were higher in compulsive water drinkers, who subsequently drank more water than in either diabetes insipidus (P less than 0.01) or controls (P less than 0.001). Drinking rapidly lowered thirst ratings in controls and diabetes insipidus before changes occurred in plasma osmolality, but remained elevated in patients with compulsive water drinking. Linear regression analysis defined a lower osmotic threshold for thirst in compulsive water drinking compared with controls or diabetes insipidus. CONCLUSIONS There are abnormalities of the osmotic stimulation and non-osmotic inhibition of thirst in compulsive water drinking, suggesting that the underlying defect is one of interpretation of osmotic and non-osmotic inputs. Measurement of thirst responses during hypertonic saline infusion and subsequent water drinking may provide useful diagnostic information in the differentiation of polyuric states.