DHEA and its sulfate ester DHEAS are the most abundant steroids in the human circulation. Only desulfated DHEA is biologically active and can be converted downstream toward sex steroids. The current concept is that DHEAS serves as the hydrophilic storage pool for DHEA regeneration and that DHEA and DHEAS are interconverted freely via hydroxysteroid sulfotransferases and steroid sulfatase. Here we sought to analyze DHEA/DHEAS interconversion in 16 healthy young and elderly men (n = 8 in each group; ages 23 –29 and 52 –66 yrs, BMI 20– 26 kg/m 2 and 23– 28 kg/m 2 , respectively). They were studied with frequent serum sampling (0830 h –1500 h) on three occasions: at baseline, after oral administration of 100 mg DHEA at 0900 h, and after i.v. administration of 25 mg DHEAS at 0900 h. Oral DHEA and i.v. DHEAS resulted in similar long-standing increases in serum DHEAS (oral DHEA versus i.v. DHEAS: AUC0-6 h 98 ± 9 versus 95 ± 7 mmol/lxh, n.s.). Oral DHEA also led to a significant increase in serum DHEA (AUC0-6 h 400 ± 32 versus 263 ± 20 nmol/lxh at baseline, p < 0.05). However, surprisingly, DHEAS i.v. did not result in any significant DHEA increase (AUC0-6 h 295 ± 20 versus 263 ± 20 nmol/lxh at baseline, n.s.). Analysis of downstream conversion revealed a similar pattern with a significant increase in androstenedione after oral DHEA (p < 0.05) but not after DHEAS i.v. (n.s.). Similarly, androstanediol glucoronide, a marker of peripheral androgen synthesis,