BACKGROUND: Recent trials suggested that methotrexate may be effective in refractory Crohn's disease (CD). We analyzed the data of 20 patients treated with methotrexate because of corticodependent or refractory CD. METHODS: Between January 1995 and June 1997, 20 azathioprine-resistant or -intolerant patients with active CD requiring continuous glucocorticosteroid treatment were treated with parenteral methotrexate. Clinical response was assessed by the Harvey-Bradshaw clinical activity index. Concomitant steroid use and steroid withdrawal rates were recorded. Patients were assessed at 12 weeks, 6 months, 9 months, and 12 months after the start of methotrexate therapy. RESULTS: At 12 weeks, a clinical response was obtained in 14/20 patients (70%). These response rates decreased to 10/20 patients at 6 months, 8/17 patients at 9 months, and 4/14 evaluable patients at 12 months. In initial responders (n = 14), maintenance of remission was observed in 9/14, 6/11, and 3/9 patients at 6, 9, and 12 months, respectively. Methotrexate allowed corticosteroid tapering in 85% of patients and discontinuation in 60% of patients at 6 months. Side effects were rather frequent but usually mild and prompted discontinuation in two patients. CONCLUSIONS: In this retrospective study, parenteral methotrexate appeared to be effective in inducing a clinical response in 70% of azathioprine-resistant or -intolerant CD patients and often permitted corticosteroid tapering, with an acceptable short-term toxicity. The potential of methotrexate to maintain long-term remission in refractory patients, however, appears less convincing.