The levels of dehydroepiandrosterone (DHEA) and its sulfate ester DHEAS decrease,with age after a peak,around,25 yr. Animal,studies as well as the first studies in humans,have,generated,the idea that DHEA replacement,in elderly subjects may,have,beneficial effects on well-being and,cognitive,functions. In the present,experiment,40 healthy elderly men and women (mean age, 69 yr) participated in a double blind, placebo-controlled DHEA substitution study. For 2 weeks subjects took 50 mg DHEA daily, followed by a 2-week wash-out period,and,a 2-week placebo,period. The treatment,sequence,was randomized in a cross-over design. After 2 weeks of DHEA or placebo, psychological,and,physical,well-being as well as cognitive,perfor- mance,were,assessed,using several questionnaires,and neuropsycho- logical tests. All subjects,had,low DHEAS baseline,levels. DHEA substitution,lead to a 5-fold increase in DHEAS levels in women,(from 0.67 6 0.1 to 4.1 6 0.4 mg/mL; P , 0.001) and men (from 0.85 6 0.1 to 4.5 6 0.4 mg/mL; P , 0.001). DHEA, androstenedione, and testos- terone levels also increased significantly in both sexes (all P , 0.001). No significant changes,were,observed,in insulin-like growth,factor I or insulin-like growth,factor-binding protein-3 levels. DHEA replacement,had,no strong beneficial effect on any of the measured,psychological,or cognitive parameters.,Only women,tended to report an increase in well-being (P 5 0.11) and mood (P 5 0.10), as assessed,with,questionnaires.,They also showed,better performance in one of six cognitive tests (picture memory) after DHEA. However,