The aims of this study were to develop a rat model of hyperthyroidism and to determine the efficacy of alendronate in the prevention of thyroid hormone-induced bone loss. Ten week-old Sprague-Dawley rats injected with thyroxine 250 micrograms/kg/day (+T4) or vehicle (-T4) were treated with alendronate (+ALN) or vehicle (-ALN) orally 0.5 mg/kg/day. After 3 weeks of treatment histomorphometric parameters of cancellous bone remodeling were assessed in the proximal tibia and in the first lumbar vertebra. In the secondary spongiosa of the tibia T4 treatment caused significant bone loss, associated with increased bone turnover; trabecular bone volume, trabecular thickness and trabecular number were significantly decreased. Osteoid and osteoclast surfaces increased in +T4/-ALN as compared to control. Alendronate prevented the increase in bone turnover and increased bone volume above control values without interfering with the recruitment of osteoclasts. These changes were not apparent in the vertebra. It is concluded that excess thyroid hormone in the rat induces high turnover bone loss in the tibia which can be prevented by alendronate through an inhibition of osteoclastic activity. The lack of effects of thyroid hormone on the vertebra may be ascribed to a lower rate of basal bone turnover at that site.