Eighty-five patients with active ankylosing spondylitis (AS) were randomized to receive either sulfasalazine (less than or equal to 3 gm/day, mean 2.5) or placebo for 26 weeks. There was a statistically significant improvement, compared with baseline, in most of the clinical variables in patients receiving the active drug. Laboratory parameters (erythrocyte sedimentation rate, C-reactive protein, IgG, IgM, and IgA) also improved during the active treatment, suggesting a beneficial effect of sulfasalazine on AS. At the end of the treatment, significant differences between the sulfasalazine and placebo groups were observed in morning stiffness, chest expansion, erythrocyte sedimentation rate, and in all immunoglobulin classes. Two patients in each treatment group discontinued the trial because of side effects. Enteric-coated sulfasalazine seemed to be effective and well tolerated in patients with active AS.