Objective To compare the effect of two glucocorticosteroid enemas, budesonide and prednisolone, on adrenal gland function in patients with active distal ulcerative colitis. Design A randomized, controlled, investigator-blind study. Setting A multicentre study among outpatients from three Danish gastroenterology departments participating in a Scandinavian multicentre study. Patients The study included 26 patients with active distal ulcerative colitis, with a median disease duration of 6.5 years and a median duration of the current disease exacerbation of 26 days. Intervention Bedtime retention enemas, budesonide (2 mg/100 ml), or prednisolone disodium phosphate (25 mg/100 ml) were administered daily for up to 8 weeks. Adrenocorticotropic hormone (ACTH) tests were performed at entry and after 4 and 8 weeks of treatment. Results Baseline plasma cortisol values were significantly suppressed after 4 and 8 weeks of prednisolone treatment, but remained unchanged during budesonide treatment. In the prednisolone group at weeks 4 and 8, plasma cortisol levels were below 500 nmol/l 30 min after ACTH injection in eight out of 14 and four out of nine patients, respectively. By contrast, the ACTH tests were normal in the budesonide-treated patients. Conclusion Budesonide enema is as effective as prednisolone enema in the treatment of active distal ulcerative colitis and does not suppress adrenal gland function.