Promethazine HCl (Phenergan) was added to the drinking water (2.4–9.6 mg/kg/day) of castrated adult male Holtzman rats. One group of castrates and a group of normal rats received no drug and served as controls. Treatment was started at castration and continued for 4 months. After controlling for body weight, analyses of covariance and Student-Newman-Keuls tests revealed that promethazine did not prevent the development of femoral osteoporosis in the castrate rats. However, control rats (normal and untreated castrates) had significantly wider femora and thicker cortices at midshaft than did promethazine-treated animals. The results indicated that promethazine HCl had no effect on the development of femoral osteoporosis and retarded normal femoral expansion in the adult castrate male rat