Recombinant IGF-I was infused seal at a dose of 20 micrograms-kg 1-h 1 to 2 healthy subjects during a total of 79 h. Serum levels of IGF-I rose from 93 and 177 to 502 and 616 micrograms/l, respectively. Fasting blood glucose remained normal. During the infusion glomerular filtration rate increased by 31%, in subject No. 1 and by 32% in subject No.2. Concomitantly, renal plasma flow increased by 26% and 22%, respectively. Proximal and distal tubular reabsorption of fluid and sodium as determined by lithium clearance was elevated to a similar extent. When determined again one week after the end of the IGF-I infusion, all parameters of renal function had returned to baseline. Sodium excretion, body weight and blood pressure did not change. We conclude that IGF-I infused at pharmacological doses has marked effects on kidney function. Future studies will necessary to define the clinical potential of recombinant IGF-I in the treatment of diseases characterized by impaired renal perfusion and filtration.