The effect of estrogen replacement on ovariectomy-induced bone loss was evaluated in mature Sprague-Dawley rats. Undecalcified tibia of ovariectomized rats were processed for quantitative histologic assessment of cancellous bone in longitudinal sections from the primary and secondary spongiosa of the proximal metaphysis. Bone content in tissue specimens was quantified as the parameter B. Ar, two-dimensional bone mineral area. Estrogen, supplied as orally administered conjugated equine estrogens, prevented bone loss through 6 weeks of treatment. The effect of conjugated equine estrogens was dose-dependent, with significant protection against bone loss observed at doses of 10 micrograms/kg/day and higher.