We assessed serially the bone mineral loss in 37 premenopausal women for 24 months after oophorectomy and determined the dose-response for conjugated estrogen therapy in preventing this loss. Spinal cancellous bone was measured by quantitative computed tomography and measurement of appendicular cortical bone by radial photon absorptiometry and metacarpal radiogrammetry. For the placebo and low-dose treatment groups, the mean annual bone mineral losses were 7% to 9% from the vertebral spongiosum and 1% to 3% from the peripheral cortex. The correlation between axial and appendicular loss was weak (r = 0.581), precluding a reliable estimate of spinal loss from peripheral measurements. For the maximal-dose group (0.6 mg/d), the mean annual bone mineral losses were less than 0.5% from the axial and appendicular sites, and were not significant. The results indicate that spinal quantitative computed tomography provides a highly sensitive measurement of bone mineral loss after oophorectomy, that bone mineral loss is five- to sevenfold greater from the spinal spongiosum than from the appendicular cortex, and that conjugated estrogen in doses of less than 0.6 mg/d are inadequate to prevent the vertebral mineral loss.