Osteopenia is common in preterm babies, but its pathogenesis is uncertain. In this study bone density in babies was quantitated, postnatal bone mineralization compared to expected intrauterine bone mineralization and the pathogenesis of osteopenia investigated. Healthy babies (103 term, 76 preterm) were examined clinically, biochemically and radiologically the day after birth and at a time corresponding to expected full term gestation. Appendicular bone density was quantitated by magnification radiogrammetry, using the humeral cortical index (CI). The CI of preterm and term babies was similar the day after birth. In preterm babies elevated serum alkaline phosphatase and high urinary hydroxyproline indicated increased bone turnover. The CI of preterm babies at expected full term gestation was lower (p = 0.0001) than that of term babies at birth, implying that postnatal bone mineralization lagged behind expected intrauterine bone mineralization. Radiologic data suggested increased endosteal resorption rather than decreased bone formation. At expected full term gestation the preterm babies had higher serum alkaline phosphatase and urinary calcium, phosphate, c-AMP and hydroxyproline (p = 0.0001) than term babies at birth, and 15% had periosteal reactions. The biochemical as well as the radiologic data therefore indicated high turnover osteopenia in preterm babies. We conclude that postnatal bone mineralization in preterm babies lagged significantly behind expected intrauterine bone mineralization and that the osteopenia observed in preterm babies is caused by increased bone resorption and not by decreased bone formation. The cause(s) of this high turnover osteopenia, however, remains to be ascertained.