The aim of our study was to investigate adrenocortical function in the context of disease activity and inflammatory status in premenopausal RA females. Adrenal glucocorticoid and androgen responses to the 1 microg ACTH 1-24 test were investigated in 23 premenopausal RA and in 15 age- and BMI-matched healthy females. Twelve RA patients were on low-dose prednisone (<8.5 mg/day). Patients with DAS28>3.2 had lower (p<0.05) total plasma cortisol, 17-hydroxyprogesterone, dehydroepiandrosterone and androstenedione responses in the ACTH test compared to healthy controls. Patients with DAS28>3.2 had lower (p<0.05) dehydroepiandrosterone response in the ACTH test compared to patients with DAS28</=3.2. C-reactive protein (CRP), DAS28, and interleukin (IL)-6 negatively correlated with androstenedione response to ACTH 1-24. Responses of all measured adrenal steroids were lower (p<0.05) in patients on low-dose glucocorticoids compared to healthy controls. RA patients not treated with glucocorticoids had lower total cortisol response (p=0.038) but did not differ in free plasma cortisol in the ACTH test. The results indicate an association of increased disease activity with a decrease in adrenal androgen production in RA and normal cortisol bioavailability in patients not treated with glucocorticoids.