Etodolac is a new nonsteroidal anti-inflammatory drug (NSAID) with potent analgesic and antiarthritic properties. The purpose of these randomized, double-blind, parallel-group studies was to compare etodolac with other standard NSAIDs or placebo for the treatment of rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. Results of rheumatoid arthritis and osteoarthritis studies showed etodolac (200 to 300 mg b.i.d. or 200 mg t.i.d.) to be comparable to naproxen (500 mg b.i.d.), piroxicam (20 mg once daily), and diclofenac (50 mg t.i.d.). Key efficacy variables improved significantly (p less than or equal to 0.05) in all treatment groups, and there were no significant between-group differences. Studies comparing etodolac (200 mg b.i.d.) with indomethacin (50 mg t.i.d.) for treatment of ankylosing spondylitis showed significant improvement from baseline in both the patient's and physician's global assessments for both treatments. Titrated-dose studies compared etodolac (50 to 200 mg b.i.d.) with naproxen (250 to 375 mg b.i.d.) and placebo for the treatment of ankylosing spondylitis. Both active drugs resulted in greater improvement than did placebo in the patient's and investigator's global assessments. These results indicate that etodolac is as effective as naproxen, piroxicam, and diclofenac for the treatment of rheumatoid arthritis and osteoarthritis. Moreover, it is comparable to naproxen and indomethacin and superior to placebo for the treatment of ankylosing spondylitis.