1. The effect of zinc compounds on bone components in the femoral-metaphyseal tissues from elderly female rats (50 weeks old) was investigated in vitro. Bone tissues were cultured for 24 hr in Dulbecco's modified Eagle medium containing either vehicle or zinc compounds (10[-7] to 10[-5] M). 2. Zinc content, alkaline phosphatase activity, deoxyribonucleic acid (DNA) and calcium contents in the metaphyseal tissues were significantly increased by the presence of zinc sulfate (10[-6] and 10[-5] M), beta-alanyl-L-histidinato zinc (AHZ; 10[-6] and 10[-5] M) and zinc acexamate (10[-7] to 10[-5] M). At 10[-5] M, the effect of zinc acexamate on the increase of bone components was more potent than that of zinc sulfate or AHZ. 3. The effect of zinc acexamate (10[-5] M) on the increase of alkaline phosphatase activity in the metaphyseal tissues was remarkable as compared with that of insulin (10[-8] M), estrogen (10[-9] M), insulin-like growth factor-I (10[-8] M), transforming growth factor-beta (10[-10] M), sodium fluoride (10[-3] M), dexamethasone (10[-7] M) and vitamin K2 (menaquinone-4; 10[-5] M) with an effective concentration. 4. The stimulatory effect of zinc acexamate (10[-5] M) on alkaline phosphatase activity and calcium content in the metaphyseal tissues was completely blocked by the presence of dipicolinate (10[-3] M), a chelator of zinc ion, and of cycloheximide (10[-6] M), an inhibitor of protein synthesis. 5. The present study demonstrates that zinc acexamate has a potent anabolic effect on bone components in the femoral-metaphyseal tissues from female elderly rats in vitro. The effect of zinc acexamate may be based in part on protein synthesis related to zinc ion in bone cells.