In patients on antiepileptic drugs, bone loss has been mainly demonstrated at radial sites using old technology and has been ascribed to drug-induced vitamin D deficiency rather than to any direct effects of the treatment on bone cells. We examined 38 epileptic patients (24 women and 14 men) aged 20-49 years who were using either carbamazepine or phenytoin or both. Bone mineral density (BMD) at the lumbar spine and three femoral sites was measured by dual-energy x-ray absorptiometry (DXA) and serum and urine markers of bone and mineral metabolism were determined. The latter included the C-terminal extension peptide of type I procollagen (PICP), a putative serum marker of bone formation, and the cross-linked carboxyl-terminal telopeptide of human type I collagen (ICTP), a novel serum marker of bone matrix degradation. In female patients on phenytoin, weight- and height-adjusted BMD was reduced at the femoral neck and the Ward's triangle (p < 0.05) but was at the control level in the other patient groups at all four measurement sites. Compared with controls, the serum concentrations of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were reduced by 26% (p < 0.01) and by 27% (p < 0.001) in female patients. These changes were independent of the therapy used. They were not present in male patients. For both genders the serum levels of vitamin D binding protein were normal. Both female and male patients had hypocalcemia, but women only showed hypocalciuria.(ABSTRACT TRUNCATED AT 250 WORDS)