OBJECTIVE Splanchnic arterial vasodilatation has been causally related with hyperdynamic circulation and impaired natriuresis in advanced cirrhosis and has also been suggested to be responsible for the subtle sodium retention in pre-ascitic cirrhosis. This study evaluated the effects of a 7-day treatment with the alpha1-adrenergic agonist midodrine in non-azotemic cirrhotic patients with and without ascites. METHODS Thirty-nine cirrhotic patients were studied at baseline and 7 days after administration of oral midodrine 10mg, t.i.d. (11 without and 12 with ascites) or placebo (8 without and 8 with ascites). RESULTS A significant increase in urine sodium excretion was noted after midodrine administration in patients without and with ascites, in line with significant increases in mean arterial pressure and systemic vascular resistance, and significant decreases in cardiac output and heart rate. Significant increases in glomerular filtration rate, filtration fraction, and urine volume and significant decreases in plasma renin activity and aldosterone were observed in patients with ascites. Placebo had no effect in any study group. CONCLUSIONS The administration of midodrine for 7 days improves systemic haemodynamics and sodium excretion in non-azotemic cirrhotic patients without or with ascites. In patients with ascites, but not in those without ascites, these effects are associated with a suppression of the activity of the renin-angiotensin-aldosterone system, suggesting that the increase in natriuresis is related to the improvement in the effective arterial blood volume.