In order to investigate the pathophysiology of anticonvulsant-induced osteopenia, circulating levels of bone gamma-carboxyglutamic acid-containing protein (Bone Gla Protein: BGP) and urinary excretion of BGP were measured in 16 children on chronic anticonvulsant therapy and in 12 control children. Using microdensitometry analysis, osteopenia was found in 25% of the anticonvulsant therapy group, but it was not observed in the control group. Serum BGP and A1-P levels were significantly increased in the anticonvulsant group compared with the control group (P less than 0.05 and P less than 0.01, respectively), and a positive correlation was found between serum BGP and A1-P levels (P less than 0.05). Urinary excretion of BGP and hydroxyproline showed an increase in the anticonvulsant group, but it was not statistically significant. On the other hand, there was no significant difference between the two groups in serum levels of vitamin D metabolites, PTH, calcitonin, Ca, or P or in urinary excretion of Ca or P. It is suggested, therefore, that the increased BGP level in children receiving anticonvulsant therapy is a reflection of high bone turnover due to anticonvulsant drug complications.