Etodolac is the first of a new class of nonsteroidal anti-inflammatory drugs--the pyranocarboxylic acids--and has potent analgesic and anti-inflammatory properties. Etodolac and piroxicam were compared in the treatment of patients with active rheumatoid arthritis. A total of 118 patients entered this double-blind parallel study and were randomly assigned to receive 200 mg of etodolac twice a day (60 patients) or 20 mg of piroxicam once a day (58 patients) for 12 weeks. After the baseline evaluation, efficacy and tolerability evaluations were made at 2, 4, 6, 8, and 12 weeks. Significant improvement from baseline was noted in both treatment groups in the patient's and physician's global evaluations, in the number of swollen and tender joints, and in the pain intensity scores. Improvement was noted at the first visit (week 2) and continued through week 12. Based on changes in the patient's global evaluation, 56% of the etodolac-treated patients and 47% of the piroxicam-treated patients showed improvement at the final evaluation. Based on changes in the physician's global evaluation, 47% of the etodolac-treated patients and 42% of the piroxicam-treated patients showed improvement at the final evaluation. Eight (13%) patients in the etodolac group and 7 (12%) patients in the piroxicam group withdrew from the study because of adverse events. Most adverse events were mild to moderate; gastrointestinal complaints were the most prevalent adverse events in both treatment groups. No clinically significant changes were seen in laboratory test results or vital signs. These results demonstrate that etodolac is well tolerated and effective in the treatment of the signs and symptoms of rheumatoid arthritis and compares favorably to piroxicam in safety and efficacy.