Short-term high-dose insulin-like growth factor-1 (IGF-1) therapy has been shown to enhance glomerular filtration rate (GFR) in end-stage chronic renal failure (CRF), but the efficacy and safety of prolonged therapy is unproven. To determine if prolonged therapy with IGF-1 can enhance renal function in advanced CRF, eight patients were entered into a study to receive one month of IGF-1 treatment, 60 micrograms/kg subcutaneously b.i.d. Six patients completed the study and two dropped out for reasons considered to be unrelated to the IGF-I treatment. Baseline inulin and PAH clearances averaged 17 +/- 3 and 66 +/- 14 ml/min/1.73 m2, respectively, in the subjects who completed the study. With treatment there was a modest 14% increase in the average GFR which approached statistical significance (P = 0.051). After stopping treatment the clearance values returned to basal values. The PAH clearance showed a similar trend. There were no significant changes in BUN, serum creatinine or electrolyte levels. On the other hand there were marked changes in the serum IGF binding protein (IGFBP) profile. Serum IGFBP-3 levels fell while IGFBP-1 and -2 levels rose during treatment, changes that likely affect the bioavailability of IGF-I. Thus, in this small series of patients IGF-1 treatment produced significant changes in the serum IGFBP profile and a modest upward trend in the GFR.