Uroguanylin stimulates renal and intestinal receptor guanylate cyclase and elicits natriuresis, kaliuresis and diuresis. It is mainly produced in the intestine and circulates in plasma. Its excretion in the urine is increased by a high-sodium diet. These findings suggest that uroguanylin acts as an intestinal natriuretic factor via guanylate cyclase under sodium loading conditions. Recent studies show that uroguanylin is also produced in the kidney and is localized in the renal tubules, indicating the possibility that uroguanylin is an intrarenal paracrine factor. Using a sensitive radioimmunoassay, we measured the plasma concentrations of uroguanylin in patients with nephrotic syndrome (NS) as well as those undergoing hemodialysis, characterized by water and sodium retention. Plasma uroguanylin level as well as blood pressure and cardiothoracic ratio were higher in NS than in non-nephrotic patients. There was a significant inverse correlation between the concentration of plasma uroguanylin and that of serum total protein or albumin, indicating that the plasma concentration of uroguanylin increases with the severity of the nephrotic state. Plasma uroguanylin level in the patients with hemodialysis was significantly correlated with inter-dialytic weight gain. Taking into account its potent natriuretic effect, uroguanylin may play an important role in the regulatory mechanism of fluid retention in these patients.