The effect of zinc compounds on osteoclast-like cell formation in mouse marrow culture in vitro was investigated. The bone marrow cells were cultured for 7 days in alpha-minimal essential medium containing a well-known bone resorbing agent [1,25-dihydroxyvitamin D3, parathyroid hormone (1-34), interleukin-1 alpha or prostaglandin E2]. Osteoclast-like cell formation was estimated by staining for tartrate-resistant acid phosphatase (TRACP), a marker enzyme of osteoclasts. The presence of 1,25-dihydroxyvitamin D3 (10(-8) M), parathyroid hormone (10(-8) M), interleukin-1 alpha (50 U/mL) or prostaglandin E2 (10(-6) M) induced a remarkable increase in osteoclast-like multinucleated cells. These increases were inhibited by the presence of zinc sulfate or zinc-chelating dipeptide (beta-alanyl-L-histidinato zinc; AHZ) in the concentration range of 10(-8) to 10(-5) M. The inhibitory effect of AHZ (10(-8) and 10(-7) M) was more intensive than that of zinc sulfate. Furthermore, the presence of Ni2+, Cu2+, Mn2+ or Co2+ (10(-7) and 10(-6) M) did not have an effect on parathyroid hormone (10(-8) M)-induced osteoclast-like cell formation. The present study clearly demonstrates that zinc compounds have a potent inhibitory effect on osteoclast-like cell formation in mouse marrow culture.