Ten patients with hepatorenal syndrome were evaluated before and after creation of a side-to-side portacaval shunt or insertion of a peritoneovenous shunt, procedures which produced an increase in plasma volume and cardiac output. In the seven patients who survived surgery, renal function improved significantly, plasma renin activity fell from high to normal levels, and low levels of plasma renin substrate increased. Prior to surgery, blockade of angiotension II by saralasin produced hypotension and an increase in plasma renin activity, whereas after surgery, saralasin had no effect on blood pressure or renin. Our findings suggest that decreased "effective" plasma volume may be important in the stimulation of renin release and possibly in the pathophysiology of renal failure in the hepatorenal syndrome.