Growth retardation in children with end-stage renal disease (ESRD) is associated with normal to slightly low concentrations of insulin-like growth factor (IGF)-I and increased concentrations of IGF-binding proteins (IGFBPs) in serum. Consequently, IGF-I bioactivity is reduced in serum from uremic patients presumably due to a decrease in the concentration of free IGF-I. Improvement of linear growth with growth hormone (GH) treatment of uremic children is thought to be due to increased IGF-I/IGFBP ratio, thus resulting in increased free IGF-I levels during treatment. The purpose of the present study was to determine whether free/dissociable IGF-I levels are in fact low in uremic children and whether increased growth velocity during GH treatment is associated with an increase in the free IGF-I concentration. Serum total and free/dissociable IGF-I concentrations were measured in 5 children with ESRD before and during treatment with GH, and in control children matched for age, pubertal status, and body mass index. Height velocity increased from 3.7 ± 1.0 cm/yr to 6.5 ± 1.2 cm/yr with an increment in height SDS at the end of the first year of GH treatment. Free/dissociable IGF-I concentrations tended to be lower in uremic children compared to control children (3.0 ± 0.3 vs 7.3 ± 2.1 μg/l, respectively). During GH treatment, free/dissociable IGF-I levels increased significantly to 8.5 ± 1.0 μg/l at 3 months and 6.9 ± 1.4 μg/l at 6-24 months, p<0.05 compared to pretreatment. Total IGF-I levels were 243 ± 18 μg/l in children with ESRD before treatment and these values also increased during GH treatment (740 ± 114 μg/l at 3 months and 442 ± 44 μg/l at 6-24 months, p<0.05, compared to pretreatment). Total IGF- I concentration in the control group was 439 ± 114 μg/l. These results support the hypothesis that growth retardation in children with chronic renal failure is associated with a reduction in the concentration of free, biologically available IGF-I, and that increased growth velocity during GH treatment of these children is associated with restoration of free IGF-I concentrations.