SummaryAlthough it is known that calcitonin decreases bone resorption, lowers serum calcium and phosphate, and influences the urinary excretion of these ions, its effect upon skeletal maturation in growing children has not been elucidated. Conceivably, the higher serum calcitonin levels that have been reported in children may promote bone formation and growth.To study immunoreactive urine calcitonin (iCT) in normal children, we used the radioimmunoassay (RIA) which we had developed previously to measure the hormone in normal adults and to screen persons at risk for medullary thyroid carcinoma (MTC). The measurement of urine iCT by RIA is particularly useful for children at risk for this thyroid malignancy because it obviates the need for venipunctures. Two antisera, one having region specificity for the midportion of CT (Ab-IIIb) and the other having carboxyl terminal recognition (Ab-IV), were utilized for the assay.For the carboxylterminal antiserum (Ab-IV), boys of ages 7 to 12 years (mean urine iCT, (ng/mg ± S.D.), 0.29 ± 0.18) had urine iCT levels significantly higher than girls the same age (0.13 ± 0.05) and higher than both adult males (0.16 ± 0.07) and adult females (0.084 ± 0.034). Boys ages 13 to 15 years (0.12 ± 0.03) had urine iCT concentrations which were not different from adult males. Girls of ages 7 to 12 years (0.13 ± 0.05) had iCT levels significantly lower than boys of the same age (0.29 ± 0.18), but significantly higher than adult females (0.084 ± 0.034). Girls ages 13 to 15 (0.11 ± 0.05) had urine iCT levels not significantly different from boys of the same age (0.12 ± 0.03).For the midportion antiserum (Ab-IIIb), children ages 7 to 15 (0.58 ± 0.384) had urine iCT concentrations greater than adults (0.26 ± 0.10), but there were not significant differences in levels between boys and girls of the same age.Gel filtration studies revealed greater amounts of higher molecular weight fractions (pU-2, ∼14,600 daltons; pU-3, ∼11,000) of urine calcitonin than were found in the urine of most normal adults and all patients with MTC.Previously, we have established criteria for diagnosing MTC in adults using Ab-IV in the urine calcitonin RIA. These adult criteria can be applied to females of all ages and to males ≥12 years of age, but levels for boys <12 years require the adjusted criteria reported in this publication. In the present study, when using Ab-IV (the carboxyl terminal antiserum used in the previous MTC study), we have found higher urine iCT levels in children than among adults. The mean level in the various age groups decreased with age. Using the data obtained from this study, we can be more certain of our determination that a child between the ages of 6 and 15 is either normal or has MTC.