The use of peripheral quantitative computed tomography (pQCT) was investigated for the measurement of volumetric bone mineral density (BMD) in mg x cm-3. Two studies were undertaken. In the first study, the precision of pQCT in vivo and ex vivo was tested at 14 weeks postovariectomy (OVX). In the second study, the efficacy of a standard antiresorptive treatment, 17beta-estradiol (E2), was tested 6 weeks post-OVX. The precision for total (compact plus trabecular) BMD was 1.3-1.9%, and that for trabecular BMD was 2.4-2. 7%. There was excellent agreement between trabecular BMD measurements in vivo and ex vivo (r = 0.91). Significant reductions in trabecular BMD were observed in vivo at 14 and 6 weeks following ovariectomy in the femur, in each study. The loss of trabecular BMD depended on slice location, and varied from 0 to 22% at 6 weeks, and from 0 to 26% at 14 weeks (P < 0.001, at the affected locations). The antiresorptive effect of treatment was demonstrated in the 6-week study: there was no significant difference in BMD between sham-operated and E2-treated OVX rats.