The purpose of this study was to determine whether 17-ss-estradiol affects the rate of brain protein synthesis in ovariectomized female rats. Experiments were conducted on three groups of 12-wk-old female rats: group 1 were ovariectomized to reduce the level of plasma estradiol, group 2 were ovariectomized and treated with estradiol and group 3 were sham-operated controls. The fractional rates of protein synthesis in brain of ovariectomized rats treated with estradiol were significantly greater than that in ovariectomized rats without estradiol treatment. In the cerebral cortex and cerebellum, the RNA activity [g protein synthesized/(g RNA. d)] significantly correlated (r > 0.87, P < 0.001) with the fractional rate of protein synthesis. The RNA concentration (mg RNA/g protein) was not related to the fractional rate of protein synthesis in any organ. The results suggest that estrogen treatment of ovariectomized female rats is likely to increase the rate of protein synthesis in the brain and that RNA activity is at least in part related to the fractional rate of brain protein synthesis.