Using a highly specific SIA we have determined SmC/IGF-I in 160 healthy children and adolescents 0-16 years of age to define the normal range of our assay system. Serum samples were extracted with acid-ethanol. The SmC/IGF-I antiserum a gift of Drs. UNDERWOOD and VAN WYK, Chapel Hill, NC distributed by the NHPP Baltimore, MD. The intra assay coefficient of variance ( CV ) was 5.6%, the inter assay CV 9.8% determined at 3 dose levels. There was a slow and constant increase of SmC/IGF-I from very low levels during the first 2 years of life ( 33-30 ng/ml; x -SD ) to peak levels in the 12-14 years group in girls ( 460 ± 75 ng/ml ) and the 14-16 years group in boys ( 445 ± 213 ng/ml ), both significantly higher than levels in normal adults aged 18-25 years ( 237 ± 51 ng/ml ). From 6-8 years up to 12-14 years mean SmC/IGF-I levels were significantly higher in girls than in boys ( p < 0.01 ) SmC/IGF-I in both sexes was highest during TANNER stages III and IV. In conclusion: there is a surprisingly early and marked difference of SmC/IGF-I levels in girls and boys, which only equalize after full puberty is reached. This may be partly due to the earlier onset of puberty in girls and to the stimulatory effect of low concentrations of estrogens on the growth hormone-somatomedin axis even before clinical signs of puberty can be observed.