We surveyed both normal children and patient populations to identify the effects of metabolic bone disease and impaired renal function on serum levels of osteocalcin, a vitamin K-dependent protein synthesized in bone. Cord blood osteocalcin was nearly double that of maternal osteocalcin, but there was no correlation between the two. Infants with Apgar scores less than or equal to 7 had a lower mean serum osteocalcin value (8.7 ng/ml, n = 8) than did those with scores of 8 to 10 (16.6 ng/ml, n = 38). Serum osteocalcin elevation coincided with the pubertal growth spurt. In boys, levels decreased to adult values by 18 years of age, as do other indices of bone metabolism; in girls, the levels decreased earlier and had a less pronounced maximum. In children with renal failure, osteocalcin was substantially increased, presumably because of diminished renal clearance of the protein. Children receiving peritoneal dialysis, however, had mean serum concentrations less than half of those seen in children receiving hemodialysis (117 vs 328 ng/ml). The peritoneal dialysate contained significant amounts of osteocalcin, but none was detectable in hemodialysate. Correlation between bone disease and serum osteocalcin was evident in a longitudinal study of one patient with renal failure. Children with various forms of rickets had elevated osteocalcin levels; hypoparathyroidism and osteoporosis were accompanied by variable changes. Serum osteocalcin holds promise as a useful marker of subacute changes in bone metabolism.