Evidence has indicated that circulating adrenal steroid quantitites were significantly changed in patients with Alzheimer's disease (AD). Aside of 3 beta-sulfatation and 3 beta-acylations, levels of dehydroepiandrosterone (DHEA) result from production and metabolic transformation yields. 7 alpha-Hydroxylation of DHEA has been described in humans, and 7 alpha-hydroxy-DHEA may be responsible for the known antiglucocorticoid effects of DHEA. Using a negative ion fragmentometry method with gas chromatography/mass spectrometry on trifluoroacetate derivatives, we measured levels of free 7 alpha-hydroxy-DHEA as well as its sulfated conjugate and its fatty acid esters in serum of 10 female patients with AD and of 8 age-matched healthy control women. Free 7 alpha-hydroxy-DHEA levels in AD and controls were not significantly different (240.2 +/- 37.2 pg/ml and 206.8 +/- 21.6 pg/ml, respectively), but sulfate conjugate levels were significantly increased in AD (p = .01) (262 +/- 28.4 and 145.4 +/- 27.6, respectively) as well as fatty acid esters (p = .041) (65.7 +/- 6.9 and 40.7 +/- 9.2, respectively). These results indicated that the total 7 alpha-hydroxy-DHEA produced was significantly increased in AD (p = .024) and may contribute to the disease-related disturbances of DHEA production and metabolism.