Bone gamma-carboxyglutamic acid protein [BGP (osteocalcin)] is a protein synthesized by osteoblasts and incorporated in the bone matrix. Serum BGP is a sensitive marker of bone formation, and it parallels the growth velocity curve during childhood and adolescence. Serum BGP was measured at the age of 2, 6, and 9 mo in a cohort study of nutrition and growth in 91 healthy infants. At 2 mo, the mean BGP value (+/- SD) was 275 +/- 87 ng/mL in infants exclusively breast-fed, and 80 +/- 44 ng/mL in formula-fed infants. At 6 mo, the values were 142 +/- 58 ng/mL and 55 +/- 30 ng/mL, and at 9 mo 75 +/- 39 ng/mL and 45 +/- 19 ng/mL in partially breast-fed and formula-fed infants, respectively. The differences were significant (p less than 0.001) at all three ages. At 2 and 9 mo, breast-milk intake was measured by test-weighing. Serum BGP was positively correlated to breast milk intake (mL/kg body wt) at 2 mo (r = 0.59, p less than 0.001) and 9 mo (r = 0.41, p = 0.06). When breast-feeding was stopped, the high BGP concentrations were not sustained. There were no significant differences in linear growth velocity between breast-fed and formula-fed infants and no correlation between BGP values and linear growth velocity. We speculate that either a factor in human milk or the level of minerals in human milk causes the high BGP values. Moreover, if the higher values are associated with increased osteoblast activity, then the remodeling or the mineralization of bone might be different in infants not being breast-fed.