The natural course of renal function in patients with cirrhosis and ascites but without azotemia is unclear. Therefore, a prospective evaluation of 23 non-azotemic cirrhotic patients with ascites was carried out over a three-year interval. Assessment included evaluation of serum electrolyte values, liver function tests, plasma renin levels, and parathyroid hormone levels. Renal function was determined by measurement of clearances of water and solute excretion, and simultaneous clearances of para-amino hippurate, inulin, and creatinine. The initial mean glomerular filtration rate was 66 ml/minute, serum creatinine level was 1.1 mg/dl, and blood urea nitrogen value was 13 mg/dl. The glomerular filtration rate showed marked variability among patients. On the basis of initial glomerular filtration rate, the patients were divided into three groups. Group I consisted of patients with supranormal filtration rates (mean 183 ml/minute), Group II constituted patients with normal filtration rates (mean 92 ml/minute), and Group III comprised patients with severely impaired filtration rates (mean 32 ml/minute). The serum creatinine level was below 1.5 mg/dl in all three groups. Serial measurement of renal function was performed in 18 patients over a mean of 310 days (range four to 1,176 days). Eighty-six percent of patients studied from Groups I and II maintained a normal or supranormal glomerular filtration rate over one year. However, most patients in Group III showed a progressive decline in filtration rate, despite no change in serum creatinine value. Sixty-seven percent of Group III patients died over a mean of one year. The mean 24-hour solute excretion among Group III patients was only 263 mOsm per day, significantly less than the control value of 874 mOsm per day in other hospitalized non-cirrhotic patients. The serum creatinine level frequently failed to rise above normal even when the glomerular filtration rate was very low (less than 25 ml/minute), and creatinine clearance overestimated inulin clearance by a factor of two in Group III patients. However, the creatinine index was an aid in determining true glomerular filtration rate and may be a useful clinical test in the evaluation of renal insufficiency in cirrhotic patients with normal serum creatinine values. Many patients with cirrhosis and ascites will have a glomerular filtration rate of less than 60 ml/minute but a normal serum creatinine level. These patients may constitute a previously unrecognized large group.