Adrenal androgen production is reduced in association with disease severity in HIV-infected women. This response may be maladaptive in terms of maintenance of lean body mass, functional status and immune function. The aim of the present study was to assess whether the use of an adrenal enzyme inhibitor of 11-beta hydroxylase might increase androgen production in this population. We conducted a randomized, double-blind, placebo-controlled study of metyrapone 500 mg PO QID or placebo for 2 weeks in ten HIV-infected women with AIDS wasting (weight < 90% IBW or weight loss > 10%) and reduced androgen levels. Basal and ACTH stimulated androgen, mineralocorticoid and glucocorticoid levels were measured at baseline and after 14 days of treatment. Subjects were similar in age (40.9±0.9 years), weight (91.7±3.5%IBW) and hormone concentrations at study entry. Total testosterone (84±54 vs. -0.4±2 ng/dL, P=0.024), free testosterone (6.5±2.8 vs. 0.1±0.1 pg/mL, P=0.024), DHEA (5.0±3.2 vs. -0.6±0.5 (µg/L, P=0.024) and 11-deoxycortisol (2145±820 vs. -14±22 ng/dL, P=0.024) levels increased in response to metyrapone compared to placebo treatment. In response to ACTH, significant increases in the DHEA:cortisol ratio (174±48 vs. 3±3, P=0.008) were seen over time in the metyrapone group compared to placebo. Blood pressure and electrolytes did not change and signs of adrenal insufficiency were not apparent. These data from a short-term physiology study demonstrate that inhibition of 11B hydroxylase with metyrapone increases adrenal androgen secretion in HIV-infected women. Further studies are needed to assess the physiologic effects of this strategy to increase anabolic hormone levels in severe stress, including detailed testing to rule out the potential risk of concomitant adrenal insufficiency.