There is no pharmacological treatment to increase the glomerular filtration rate in end-stage renal disease (ESRD). The administration of 100 microgram/kg of insulin-like growth factor (IGF) I twice a day to patients with ESRD increases inulin clearance. However, its effect is short-lived and IGF-I has major side effects when given this way. To assess whether the use of a lower intermittent dose of IGF-I would effect sustained improved function with tolerable side effects we performed 1) a prospective open-labeled 24-day trial in which we enrolled five patients and 2) a 31-day randomized, double-blinded, placebo-controlled trial in which we enrolled 10 patients. Patients with ESRD [creatinine clearance of <15 ml. min-1. (1.73 m2)-1] and scheduled to initiate renal replacement therapy received subcutaneous IGF-I, 50 microgram. kg-1. day-1, or vehicle. Treatment with IGF I resulted in significantly increased glomerular filtration rates (inulin clearances) during the 3rd and 4th wk of therapy in both prospective and double-blinded studies. Vehicle had no effect. No patient required discontinuation of drug secondary to side effects. We conclude that IGF-I effects sustained improvement of renal function (clearances comparable to those generally achieved by dialysis) in patients with ESRD and is well tolerated.