During almost 12 years of development and clinical trials, diclofenac sodium has been shown to be both effective and safe as a new nonsteroidal antiinflammatory drug (NSAID) for the treatment of rheumatic diseases including ankylosing spondylitis (AS). We compared the safety and efficacy of 75, 100, or 125 mg/day of diclofenac with the same doses of indomethacin in a multicenter, randomized, parallel group trial in patients with AS. A single blind placebo washout period of 2 days to 2 weeks preceded the 13-week double blind treatment period. Both diclofenac and indomethacin produced significant (p less than 0.001) improvement from baseline for all 14 efficacy variables analyzed. There were no significant between treatment differences. Differences favored diclofenac in the frequency and the severity of adverse experiences reported and in the frequency of complaints affecting the central nervous system.