OBJECTIVE To study the efficacy and toxicity of methotrexate (MTX) for patients with ankylosing spondylitis (AS) in a 36 week, open, single observer study. METHODS Patients were selected for study if they had evidence of active disease and had failed to respond to treatment with nonsteroidal antiinflammatory drugs (NSAID) and sulfasalazine. Eleven patients entered the study, and 9 were evaluated at the end. Oral MTX (7.5-15 mg weekly) was given for at least 24 weeks; NSAID were kept at a stable dose. Efficacy was evaluated by calculating the relative difference of assessed variable between Week 0 and 24 and by patient evaluation. RESULTS Assessed variables showed good relative improvement. Four patients decided to continue MTX; 3 used a lower dose of NSAID; one stopped NSAID: Five patient patients discontinued MTX: 3 of these had disease flares and restarted MTX. Side effects were mild and reversible. CONCLUSIONS Results of our study showed that the majority of our patients with AS taking MTX had beneficial effects.