Three patients with reactive arthritis and 2 with ankylosing spondylitis resistant to therapy with nonsteroidal antiinflammatory drugs were treated with enteric coated sulfasalazine in an open trial. Significant toxicity was not observed; 1 patient discontinued sulfasalazine because of gastrointestinal symptoms. As a group, statistically significant improvement was observed in 50 foot walk time, morning stiffness, and hemoglobin concentration. One patient went into complete clinical remission, 2 improved, 1 showed no change, and 1 worsened. Asymptomatic colonic inflammation was found in each of 4 patients examined before beginning therapy. Changes in bowel pathology did not parallel changes in joint symptoms. Sulfasalazine may be a safe and useful therapeutic modality in patients with chronic reactive arthritis or ankylosing spondylitis.