In this comparative, cross-sectional study, we evaluated 55 patients with epilepsy on chronic use of antiepileptic drugs (AED); [(38 females and 17 males, 35 +/- 6 years (25 to 47)] and compared to 24 healthy subjects (17 females/7 males). Laboratorial evaluation of bone and mineral metabolism including measurements of bone specific alkaline phosphatase (BALP) and carboxyterminal telopeptide of type I collagen (CTX-I) were performed. Bone mineral density (BMD) was measured by DXA. BALP and CTX-I levels did not differ significantly between the groups. CTX-I levels were significantly higher in patients who were exposed to phenobarbital (P< 0.01) than those who were not. Patients presented BMD of both sites significantly lower than the controls (0.975 +/- 0.13 vs. 1.058 +/- 0.1 g/cm(2); p= 0.03; 0.930 +/- 0.1 vs. 0.988 +/- 0.12 g/cm(2); p= 0.02, respectively). Total hip BMD (0.890 +/- 0.10 vs. 0.970 +/- 0.08 g/cm(2); p< 0.003) and femoral neck (0.830 +/- 0.09 vs. 0.890 +/- 0.09 g/cm(2); p< 0.03) were significantly lower in patients who had been exposed to phenobarbital, in comparison to the non-phenobarbital users. In conclusion, patients on AED demonstrate reduced BMD. Among the AED, phenobarbital seems to be the main mediator of low BMD and increases in CTX-I.