The long-term tolerability and efficacy of indomethacin were evaluated in a retrospective study of 67 patients with moderate to severe rheumatoid arthritis, osteoarthritis, or ankylosing spondylitis who took the drug daily for periods ranging from three to 20 years. Only patients who had not experienced side effects during the first ten to 14 days of indomethacin therapy were included. No other anti-inflammatory agents were taken along with indomethacin. The average daily dosage ranged from 50 to 150 mg; for 81% of patients, the average daily dosage was 75 to 100 mg. Only nine (13%) of the 67 patients experienced side effects, all of which were transient and mild. Three patients had headache, five patients had gastrointestinal symptoms, and one patient had both gastrointestinal symptoms and headache. Repeated urinalyses did not reveal any significant abnormalities. There were no instances of leukopenia. A comparison of clinical and laboratory assessments at the initial and latest office visits indicated that signs of active inflammation had been well controlled by daily indomethacin therapy. Erythrocyte sedimentation rates were generally lower and hemoglobin values tended to be higher at the latest visit. Clinically, patients appeared to have benefited from the long-term administration of indomethacin with respect to both tolerability and efficacy.