The aim of the study was to investigate the hypothalamo-pituitary-adrenal (HPA) axis by ACTH stimulation test and the changes in adrenal size in acute brucellosis before and after therapy in a prospective study. Sixteen patients with acute brucellosis and 15 healthy subjects were included in the study during the last two years. Cortisol levels were assessed before, 30 and 60 minutes after ACTH (250 mu g i.v.) injection and the size of the adrenals was measured in both groups. Mean basal cortisol levels in the patients before the therapy and after the therapy were 22.1 +/- 6.9 mu g/dL and 11.3 +/- 6.0 mu g/dL, respectively. The difference was statistically significant (p < 0.001). There was also statistically significant difference for basal cortisol levels between the healthy subjects (12.2 +/- 4.6 mu g/dL) and the patients before the therapy (p < 0.001). Peak cortisol responses to ACTH were higher before the therapy in the patients with acute brucellosis (39.3 +/- 10.7 mu g/dL) than in the healthy subjects (30.4 +/- 4.8 mu g/dL, p = 0.014). However, there was no significant difference for peak cortisol levels in the patients before and after the therapy (32.7 +/- 8.0 mu g/dL). Mean basal cortisol levels and peak cortisol responses to ACTH between the patients after the therapy and the healthy controls were similar. Both the maximum width of the adrenal glands and the width of the adrenal limbs were significantly greater before the therapy compared to healthy subjects and post-treatment period. We concluded that the HPA axis is activated and the adrenal glands are enlarged in acute brucellosis, which is reduced after appropriate therapy.