Using histomorphometric analysis, we compared the effects of 7 d spaceflight (Biocosmos 1667) and 7 d tail-suspension in tibiae of 12-13 weeks old male Wistar rats. The skeletal alterations induced by both true and simulated weightlessness in the proximal tibial metaphysis consisted of an inhibition of longitudinal growth as indicated by the reduction of the primary spongiosa thickness. In both primary and secondary spongiosae, the loss of trabecular bone was more extensive in flight rats than in suspended rats. Impairment in cancellous and endocortical osteoid surfaces occurred in microgravity and 1-G conditions but with greater magnitude in the spongy space in flight rats. In suspended rats, the cancellous mineralization rate was decreased, suggesting an alteration of the formation activity. Bone resorption remained unchanged in flight rats whereas a twofold increase occurred in simulated conditions. These data support the hypothesis that mechanisms of bone loss in space are not entirely identical to those of tail-suspension model on Earth. New experiments allowing comparison between actual spaceflight and spaceflight simulations must be developed in order to explore common alterations and to understand differential mechanisms in the bone system.