• Cross-sectional studies from our institutions (Wyler Children's Hospital, Chicago, and Children's Hospital of Philadelphia) and others have shown that plasma somatomedin-C (Sm-C) concentrations rise during puberty. To determine the relationship between rising plasma Sm-C levels and the growth spurt at puberty, we undertook a longitudinal study of 11- to 18-year-old children. Twelve male and eight female subjects were followed up on a yearly basis for two to seven years (mean, 4.4 years). Height velocity, plasma Sm-C concentrations, and stage of sexual development were determined during each visit. All patients progressed normally in puberty during the study. The plasma Sm-C level rose during early puberty in each child and reached a maximal level of at least 2 U/mL in midpuberty, approximately one year after the attainment of peak height velocity. Maximal plasma concentrations of Sm-C were similar in male (3.5±0.71, mean±SEM) and female (3.5±1.46) subjects. Plasma Sm-C levels subsequently decreased slowly but remained above normal adult values for as long as four years after peak height velocity was reached. Plasma Sm-C concentrations increased steadily with increasing height velocity until peak height velocity was attained with a mean rise of approximately 0.5 U for each centimeter per year increase in height velocity. Since Sm-C levels remained elevated while height velocity decreased, there was no significant correlation between Sm-C levels and height velocity throughout puberty. These results suggest that caution is required in interpreting Sm-C concentrations during puberty; while normal pubertal levels may be in the acromegalic range for adults, a plasma Sm-C level of less than 1 U/mL in early puberty or less than 1.5 U/mL during middle to late puberty must be considered subnormal.