The present study was performed to evaluate possible interactions between estrogen and progesterone on peak cancellous bone mass. Ovariectomized (OVX) growing rats were treated with 17beta-estradiol (4.8 microg/day), progesterone (4.8 mg/day), a combination of the two sex steroids, or with vehicle for 14 days beginning 7 days after OVX. The tibiae were removed for histomorphometric analysis of the proximal metaphysis. OVX and growth each resulted in net resorption of cancellous bone at a sampling site adjusted for longitudinal bone growth. Estradiol and progesterone treatment each antagonized bone loss by inhibiting the decrease in trabecular number. Estradiol increased but progesterone had no effect on trabecular thickness. Progesterone did not influence either osteoclast number or the resorption of the pretreatment fluorochrome label. Estradiol reduced osteoclast number and inhibited label resorption, the latter change being accentuated by combination treatment. Estradiol reduced and progesterone enhanced the mineral apposition and bone formation rates. The results indicate that estradiol and progesterone have independent activities on cancellous bone turnover during growth. Whereas estradiol reduced bone turnover, progesterone had a stimulatory effect on bone formation. These findings suggest that progesterone has a role in establishing and maintaining peak cancellous bone volume during growth.