All of the steroidal anti-inflammatory drugs currently available are glucocorticoids. They exhibit both glycogenic and anti-inflammatory activities. These two activities are usually considered inseparable. This glycogenic activity is responsible for most of the adverse side effects that severely limit clinical use of currently available steroidal anti-inflammatory drugs. The purpose of this study was to determine if a steroid, 16-epiestriol, could exhibit significant anti-inflammatory activity without glycogenic activity. The anti-inflammatory activity of 16-epiestriol was determined using a modified Winter's carrageenin rat paw edema model. The glycogenic activity of 16-epiestriol was determined by a modification of Venning's methods on liver and plasma glucose concentrations. In each study, 16-epiestriol-treated animals were compared to untreated control and hydrocortisone-treated animals. In the anti-inflammatory study, 16-epiestriol was more than twice as effective as hydrocortisone, on an equimolar basis, in preventing edema. 16-Epiestriol exhibited no effect on the liver or plasma glucose concentration in the glycogenic study. 16-Epiestriol exhibited potent anti-inflammatory activity without glycogenic activity. 16-Epiestriol does not conform to classical steroidal structure-activity relationship theory.