The relative effectiveness of 6 nonsteroidal anti-inflammatory agents was studied in 33 patients with rheumatoid arthritis and 32 patients with ankylosing spondylitis in a double-blind, randomized, prospective study employing a 6-way multiple crossover design with 6 wk trials of each agent. In ankylosing spondylitis, naproxen, indomethacin and fenoprofen calcium were the most effective agents. In rheumatoid arthritis relatively little mean difference between drugs [the above 3 plus aspirin, ibuprofen, tolmetin sodium] was found. Most of this difference could be attributed to compliance factors, which favored drugs that required only a small number of pills daily. Despite the small differences in effect, patients had strong preferences. Of the patients, 85% were still taking their preferred medication after a mean follow-up of 1 yr.