Background and aims: The vasopressin analogue terlipressin is believed selectively to cause vasoconstriction by a V1-receptor stimulation. However, a possible antidiuretic effect by V2-receptors stimulation has never been ruled out. Patients and methods: 22 patients with ascites, including 7 with refractory ascites were included. The subjects were studied during a 400 mL/hour oral water load before and after infusion of 2 mg terlipressin (18 patients) or placebo infusion (4 patients). Effects on the V2 receptors were assessed by evaluating aquaporin-2 (AQP-2) excretion, free water clearance (C_H2O), urine osmolality (U-osm) and fractional distal water excretion (DFeH2O). Results: After terlipressin the excretion of AQP-2 increased by 89% (144 ng/(mmol creatinine), 95% confidence interval (CI) 73-214 ng/(mmol creatinine), p=0.001). CH2O decreased 1.05 mL/min (from 0.17 to -0.89 mL/min, p=0.001) and DFeH2O decreased 37% (19 vs. 12; 95% CI 2-11, p=0.01). U-osm increased by 27% (93 mosm/kg, 95% CI 23-164, p=0.02). Plasma sodium decreased 1.1 mmol/L (p<0.01). Conclusion: An increase in AQP-2 excretion and a decrease in CH2O and distal water excretion after terlipressin despite water loading is a clear indication of activation of the antidiuretic system (V2 receptor effect).