The aim of the study was to evaluate the efficacy of methotrexate treatment in patients with ankylosing spondylitis in a 3-year open trial. Seventeen patients, 14 men and three women (mean age 32.7+/-8.9 years), suffering from ankylosing spondylitis and non-responders to treatment with sulphasalazine, were enrolled in our study. Sixteen of them were evaluable at the end of the study. Methotrexate (7.5-10 mg/week) was administered for 3 years. Efficacy was evaluated on the basis of clinical and laboratory variables, radiographic signs of disease progression and daily dosage of indomethacin. We obtained a good and relatively prompt clinical response except for peripheral arthritis and iridocyclitis; in fact, after 3 months of methotrexate treatment a significant amelioration of the following parameters was observed: visual analogue scale for the evaluation of both night pain and general well-being, Shober's test, occiput-wall distance, fingertip to floor, erythrocyte sedimentation rate, C-reactive protein level and daily dose of indomethacin. A further improvement was obtained during the subsequent period. Radiographs of the spine and sacroiliac joints did not show any signs of disease progression. Side-effects were a transitory elevation of transaminases (four cases) and slight hypogammaglobulinaemia (one case). Methotrexate treatment may be useful in ankylosing spondylitis, but a combined treatment might be indicated for patients with peripheral arthritis.