Renal function was assessed in 13 children at a mean (+/- SD) age of 9 +/- 4.9 years who had been receiving total parenteral nutrition for 7.9 +/- 4.1 years. All children had normal blood pressure, urinary sediment, and serum creatinine concentrations (58.3 +/- 1.0 mumol/L). Glomerular filtration rate was measured by plasma clearance of diethylenetriaminepentaacetic acid labeled with indium 111. All 13 children had decreased glomerular filtration rate (65.5 +/- 11.9 ml/min per 1.73 m2; range 49.5 to 83.7). Creatinine clearance was 69.1 +/- 10.9 ml/min per 1.73 m2. No tubular damage, as assessed by beta 2-microglobulinuria, was detectable. Renal ultrasonography showed normal architecture with no evidence of nephrocalcinosis in all subjects. The kidney size was normal in seven children; six had reduced (less than -1 SD) size. No relationship was seen between the true glomerular filtration rate and diagnosis, number of episodes of infections, or antibiotics used. The duration of total parenteral nutrition was inversely correlated with the true glomerular filtration rate (r = -0.66, p less than 0.01). The decrease in glomerular filtration rate was not related to the underlying disease or to the nephrotoxic drugs used; the mechanism was not identified. We conclude that long-term total parenteral nutrition is associated with a decrease in glomerular filtration rate.