Impairment of calcium metabolism and low bone density have been found in hypothyroid adults. We investigated the effect of thyroid replacement therapy on calcium metabolism and bone mineralization in congenital hypothyroid (CH) infants and children. One hundred and 16 Caucasian CH consecutive patients were studied and were grouped according to their age: 23 patients at diagnosis, 20 at 3 mo, 24 at 6 mo, 25 at 12 mo and 24 at 36 mo. Thyroid replacement therapy was started at an initial dose of 6-8 micrograms/kg/day of L-thyroxine, and then decreased progressively. Calcium, phosphorus, magnesium, alkaline phosphatase (AP), parathyroid hormone (PTH) and osteocalcin (BGP) were measured as calcium metabolism indices. Bone mineral content (BMC) was measured at the mid-portion of the right radius AP, PTH and BGP concentrations were significantly higher in subjects at 3 mo of age (p < 0.05). This rise coincided with the end of the period of maximum dosage of L-thyroxine. Mild asymptomatic hypercalcemia was observed in 20 patients. All the other indices did not differ between age groups. BMC values and BMC annual increment were not different from those calculated for age-matched controls. We found that L-thyroxine replacement therapy does not alter bone mineralization of CH infants and children. Only a transitory increase of osteoblastic function was observed after the first few months of therapy.