The effect of zinc on protein synthesis in the femoral-metaphyseal tissues of normal and skeletally unloaded rats was investigated. Skeletal unloading was designed using the model of hindlimb suspension in rats. Animals were fed for 2 or 4 days during the unloading. [3H]Leucine was added to the reaction mixture containing the 5500 g supernatant fraction of the homogenate prepared from the femoral-metaphyseal tissues. In vitro protein synthesis was significantly decreased in the bone tissues from the rats which had undergone unloading for 2 or 4 days. When the metaphyseal tissues were cultured for 24 h in the presence of zinc sulfate (10(-5) M) or beta-alanyl-L-histidinato zinc (AHZ, 10(-5) M), zinc compounds clearly stimulated protein synthesis in the metaphyseal tissues from the 4-day unloaded rats. The zinc effect was also seen in the metaphyseal tissues from normal rats. The addition of zinc sulfate (10(-5) M) or AHZ (10(-7) to 10(-5) M) into the reaction mixture containing the 5500 g supernatant fraction of metaphyseal homogenate from normal or unloaded rats produced a significant increase in protein synthesis. This increase was clearly inhibited in the presence of cycloheximide (10(-7) M). The present result demonstrates that protein synthesis is impaired in the femoral-metaphyseal tissues of rats with skeletal unloading, and that this impairment is clearly restored by zinc supplementation.