Past measurements of somatomedins in chronic renal failure have yielded conflicting results because compounds that accumulate in renal failure and interfere with the somatomedin assays were not removed from assay systems. After serum somatomedins were separated from inhibitory substances by acid chromatography, we measured levels of the major somatomedins, insulin-like growth factor (IGF)-1 and IGF-2, in 16 prepubertal children with chronic renal insufficiency and in 16 age- and sex-matched normal children. Radioimmunoassayable IGF-1 levels were 220 +/- 182 (mean +/- SD) ng/mL in children with renal disease, not significantly different from levels of 248 +/- 155 ng/mL found in normal children. Levels of the less potent mitogen IGF-2, measured by radioreceptor assay, were 661 +/- 213 ng/mL in children with renal disease and were significantly greater than those of 433 +/- 139 ng/mL found in normal children (P less than .05). Since all 16 children with renal disease exhibited significant growth delay, we conclude that low serum IGF levels are unlikely to play a role in this growth failure. Further, since unsaturated somatomedin carrier proteins can interfere with the assay and in vitro biologic actions of the IGFs, and since there was more unsaturated carrier protein binding of IGF-1 by the sera of 15 children with renal disease v 15 normal children (17 +/- 3% v 12 +/- 3% binding of [125I]-IGF-1/50 muL serum, P less than .05), we suggest that somatomedin carrier proteins should be evaluated for their role in the growth failure of children with chronic renal failure.