OBJECTIVE: To investigate the hypothalamic-pituitary-adrenal (HPA) axis via the insulin-tolerance test (ITT), standard-dose (250 mu g) ACTH test (SDT) and low-dose (1 mu g) ACTH test (LDT) in patients with ankylosing spondylitis (AS). DESIGN: The study group included 13 male patients with AS who were diagnosed according to the Modified New York criteria, and 8 healthy male subjects and was carried out at the Department of Physical Medicine and Rehabilitation, Erciyes University Medical School. ACTH stimulation tests were carried out by using 1 mu g and 250 mu g i.v. ACTH as a bolus injection, and blood samples were drawn at 0, 30 and 60 min. ITT was performed by using intravenous (i.v.) soluble insulin, and serum glucose and cortisol levels were measured before and after 30, 60, 90 and 120 min. All of the tests were performed consecutively with 3-day intervals, after an overnight fast. RESULTS: There were no significant differences between the patients with AS (mean age 36.9+/-6.7 years) and the healthy subjects (mean age 37.4 +/- 5.7 years) in terms of age. The basal cortisol levels in the AS group measured during LDT, SDT and ITT (556 +/- 204 nmol/l; 524 +/- 169 nmol/l; 418 +/-232 nmol/l, respectively) were comparable to the values of the control group (572 +/- 199 nmol/l; 520 +/- 182 nmol/l; 424 +/- 194 nmol/l, respectively). There were also no significant differences in peak cortisol responses between the two groups using LDT (patients 1025 +/- 339 nmol/l; controls 844 +/- 236 nmol/l), SDT (patients 1082 +/- 243 nmol/l; controls 1120 +/- 131 nmol/l) and ITT (patients 834 +/- 256 nmol/; controls 820 +/- 239 nmol/). CONCLUSION: In contrast with findings in other inflammatory diseases such as rheumatoid arthritis and polymyalgia rheumatica, the present data indicate that there is no apparent abnormality of the HPA axis activity in patients with AS.