Apart from having written an inglorious chapter in the history of medicine, thalidomide is currently being intensely studied because of its multidimensional activity. The aim of this study was to examine the effects of thalidomide on the skeletal system in ovariectomized and non-ovariectomized rats. The experiments were carried out with female Wistar rats, divided into eight groups: sham-operated control rats; sham-operated rats receiving thalidomide at doses of 15, 30 or 60 mg/kg, po; ovariectomized control rats; ovariectomized rats receiving thalidomide at doses of 15, 30 or 60 mg/kg, po. The drug was administered for 4 weeks. Body mass gain and the mass of the uterus, liver, spleen and thymus were studied. Macrometric parameters and content of mineral substances, calcium and phosphorus in the femur, tibia and L-4 vertebra and histomorphometric parameters of the femur and tibia were examined. In the femur, the mechanical properties of the whole bone and of the femoral neck were examined. Thalidomide did not affect the skeletal system of the non-ovariectomized rats. Bilateral ovariectomy induced osteoporotic skeletal changes in mature female rats. The effects of thalidomide on the skeletal system of ovariectomized rats depended on the dose used. With a dose of 15 mg/kg, po, thalidomide counteracted some osteoporotic changes induced by estrogen deficiency. With a dose of 60 mg/kg, po, thalidomide intensified the destructive effects of estrogen deficiency on the rat skeletal system.