Serum osteocalcin (Gla) and skeletal alkaline phosphatase (SAP) concentration both reflect osteoblast activity in the dynamic process of bone formation. To assess the relation in premature infants between change in bone mineral content (BMC) and both Gla and SAP serum concentration, we longitudinally measured BMC via photon absorptiometry and serum Gla and SAP concentration from birth to 16 wk in 20 very low birth weight infants. Serum total calcium, phosphorus, parathyroid hormone, and vitamin D metabolite concentrations were also monitored. All serum values were measured in the 20 mothers at delivery. Cord blood Gla concentrations were significantly (p less than 0.03) greater than maternal levels, and by 1 wk had significantly (p less than 0.001) increased from birth values. Total calcium, parathyroid hormone, phosphorus, and vitamin D concentrations remained in the normal range throughout the study. The increase in serum Gla concentrations, birth to 1 wk, were significantly correlated with the simultaneous increase in 1,25-dihydroxyvitamin D concentrations. The correlation between the change in BMC, however, over the first 4 mo of life and both Gla and SAP serum concentrations failed to reach statistical significance. Finally, a significant (p less than 0.003) negative correlation was measured between serum Gla and SAP concentrations at wk 4, and, although not significant, a consistently negative correlation was measured from 1-16 wk of age.(ABSTRACT TRUNCATED AT 250 WORDS)