The decrease in estrogen levels that follows the onset of menopause causes rapid bone loss, resulting in osteoporosis. However, the mechanism by which this occurs remains unclear, especially concerning the regulation of osteoclasts, i.e. the bone-resorbing cells. Using a pit assay involving isolated mature osteoclasts from rabbit long bones, we found that estrogen inhibited the bone-resorbing activity in a dose- and time-dependent manner. Furthermore, we clarified by Northern analysis that estrogen down-regulated the mRNA levels of cathepsin K/OC-2 and that putative estrogen receptor (ER) mRNA was expressed in these osteoclasts. Moreover, other sizes of mRNAs that hybridized with ER cDNA probe were found in these cells. Our results suggest that osteoclasts may be indeed target cells for estrogen and that estrogen might regulate a part of bone metabolism through osteoclasts.