Abstract. Data from animal and in vitro studies suggest that the growth-promoting effects of the adrenal androgen dehydroepiandrosterone sulfate (DHEAS) may be mediated by stimulation of insulin-like growth factor-I (IGF-I) and/or inhibition of interleukin 6 (IL-6), a cytokine mediator of bone resorption. This study tests the hypotheses that there are effects of age on serum DHEAS, IGF-I, and IL-6 levels, and that levels of IGF-I and IL-6 are related to DHEAS levels. The study included 102 women: 27 premenopausal and 75 postmenopausal, including 35 postmenopausal women with osteoporosis, as defined by bone mineral density scores by dual X-ray energy absorptiometry. DHEAS levels decreased significantly with age (r =0.52, P 0.0001) and IGF-I levels decreased significantly with age (r =0.49, P 0.0001). IL-6 levels increased significantly with age (r = 0.36, P= 0.008). IGF-I was positively correlated to DHEAS levels (r = 0.43, P 0.0001, n = 102) and IL-6 levels were negatively correlated to DHEAS levels (r =0.32, P= 0.021, n = 54). Levels of DHEAS and IGF-I were correlated with T scores of the spine and some hip sites. In a multiple variable model to predict DHEAS, age was an important predictor (P 0.001), but osteoporosis status, IGF-I, and IL-6 were not. The median DHEAS level was lower in the postmenopausal osteoporotic women (67 g/dl, n = 35) than in the nonosteoporotic postmenopausal women (106.3 g/dl, n = 40, P= 0.03), but this was not significant after correction for age. Age accounted for 32% of the variance in DHEAS levels. In summary, DHEAS levels decreased with age and had a positive association with IGF-I levels and a negative association with IL-6 levels. DHEA deficiency may contribute to age-related bone loss through anabolic (IGF-I) and anti-osteolytic (IL-6) mechanisms.