Serum levels of insulin-like growth factor-I (IGF-I), IGF-II, and IGF binding protein-1 (IGFBP-1), IGFBP-2, and IGFBP-3 were measured in 54 children with end-stage renal disease (ESRD). The results were compared with their respective age-dependent normal ranges. IGFs and IGFBPs were quantified by specific radioimmunoassay. Serum IGF-I in children with ESRD tended to cluster in the low-normal range. Mean age-related serum IGF-I levels were slightly, but significantly decreased (-1.08 +/- 0.17 SDS). In view of the prevailing elevated growth hormone levels in ESRD, these serum IGF-I levels must be interpreted as inadequately low. In contrast to IGF-I, individual serum IGF-II levels were either in the upper-normal range or clearly elevated. Mean age-related IGF-II (1.09 +/- 0.15 SDS) was slightly, but significantly elevated. Mean age-related IGFBP-1 serum levels (2.20 +/- 0.10 SDS) were moderately increased, while mean age-related serum IGFBP-2 (5.65 +/- 0.36) and IGFBP-3 levels (3.60 +/- 0.19) were markedly elevated. Affinity cross-linking of 125iodine-IGF-II to sera from patients with ESRD and immunoprecipitation with a specific antiserum showed that low molecular weight IGFBP-3 fragments in ESRD serum are capable of binding IGF. In patients with ESRD, a rapid and persistent decline of immunoreactive IGFBP-3 in response to restoration of renal function by renal transplantation was observed. This finding indicates that renal dysfunction contributes to high immunoreactive IGFBP-3 levels in ESRD. In conclusion, the imbalance between normal total IGF levels and the excess of IGFBPs in ESRD is likely to play a role in growth failure in these children.