A 12-week double-blind randomized drug trial followed by an open extension period of 36 weeks was carried out in 38 male patients with ankylosing spondylitis (AS) to compare the efficacy and safety of diflunisal (500 mg twice daily) and phenylbutazone (200 mg twice daily). Both drugs proved to be effective in improving the severity of symptoms associated with AS, and this improvement was maintained throughout the open extension period. Initially diflunisal had a more pronounced and rapid analgesic action, whereas phenylbutazone was more effective in increasing axial mobility. During the study 9 patients dropped out: 3 in each treatment group due to side effects and 1 in each group due to lack of efficacy; another patient was lost to follow-up. The two drugs were similarly safe as judged by the occurrence of adverse clinical effects, mainly gastrointestinal. This study again demonstrates the value of phenylbutazone in AS but, taking into account the possible haematological side effects, the use of other NSAIDs is stressed. Diflunisal is an alternative capable of improving the painful stiffness associated with AS.