The decline of the production of several hormones with age has been recently linked to several degenerative processes related to aging including osteoporosis. The aim of our study was to confirm the observations published in 1994 suggesting that postmenopausal women with DHEAS levels below a certain limit have a much higher risk of osteoporosis than those with the levels above this limit. The DHEAS levels were measured by RIA and compared to our own age-adjusted reference ranges. The values lower than 25th quantile were considered "subnormal". More than 500 postmenopausal subjects were included in our study. In those with "subnormal" levels bone mineral density (BMD) was measured on DEXA (Lunar or Hologic). Decreased BMD ranging from osteopenia to severe osteoporosis was found in 86% of 74 women with "subnormal" DHEAS, while the expected frequency in our postmenopausal population may be about 30%. In the following period the serum DHEAS levels were compared with DEXA findings in another 134 postmenopausal women. The DHEAS levels in all stages of decreased BMD were significantly lower than those in the group with normal BMD. The clinical sensitivity and specificity of DHEAS as a marker of increased risk of osteoporosis has been calculated for a cut-off limit of 0.5 MoM. In the light of these findings we believe that the robust and relatively cheap DHEAS determination could help us to identify women who are at higher risk of osteoporosis. Also, in the future, only the women with evidently deficient DHEA production might possibly become candidates for eventual DHEA substitution.