• Serum somatomedin-C (Sm-C) levels increase sharply during puberty, leading to difficulty in the interpretation of Sm-C values obtained from children who exhibit a discrepancy between chronological age (CA) and pubertal development. To evaluate the utility of assessing Sm-C levels on the basis of bone age (BA), we measured serum Sm-C levels in 44 boys with constitutional delay of growth (CDG). Levels of Sm-C were compared with the normative data of the Nichols Institute Reference Laboratories (NIRL), Los Angeles, by age category, substituting BA for CA. We found the mean Sm-C level in boys with CDG to be lower than that for NIRL normal subjects in each age category for both CA and BA, but the regression curve for Sm-C levels based on BA more closely approximated the NIRL regression curve than did the curve based on CA. The rise in Sm-C levels observed in NIRL normal subjects between CA 13 to 14 years is delayed in boys with CDG until CA 15 to 17 years only when a correction for BA is not made. We conclude that in boys with CDG, Sm-C levels should be interpreted on the basis of BA rather than CA, especially during the peripubertal period. The observation of blunted Sm-C levels in all age categories, even when BA was used, suggests that short children with presumed CDG may be at high risk for a "nonclassic" form of growth hormone deficiency.