The plasma level of dehydroepiandrosterone (DHEA) decreases gradually along with aging. The beneficial effects of DHEA as an anti-aging steroid, such as the stimulatory effect on immune system, anti-diabetes mellitus, anti-atherosclerosis, anti-dementia, anti-obesity and anti-osteoporosis have been demonstrated in experiment both in vitro and in vivo. It is important to investigate the effective mechanism of DHEA in therapeutics for postmenopausal osteoporosis. Having isolated and cultured osteoblasts (OBs) and osteoclasts (OCs), we analysed the effect of DHEA on osteoblastic viability, regulation of DHEA on the expression of osteoprotegerin (OPG)/receptor activator of NF-kappaB ligand (RANKL) mRNA in OBs, and then observed the action of DHEA on bone resorption of OCs in the presence or absence of OBs. The results showed that DHEA improved viability of OBs within the concentration range of 0.01-1 microM, especially at the concentration of 0.1 microM. DHEA could apparently increase the ratio of OPG/RANKL mRNA in OBs. In the presence of OBs, DHEA could decrease the number and area of absorption lacuna of specula. We concluded, therefore, only in the presence of OBs, DHEA could inhibit the bone resorption of OCs, which may be mediated by OPG/RANKL of OBs.