Controlled short-term studies (< 6 months) have yielded conflicting results as to the steroid-sparing effect of methotrexate (MTX) and its effectiveness in treating patients with chronic corticosteroid-dependent asthma (CDA). In an open study, we treated 13 patients with MXT (7.5-20 mg.week-1) for > or = 12 months (range 54-72 weeks). After 12 weeks of treatment, the intake of steroids had fallen by 36 +/- 22% (mean +/- SD); the clinical score was not significantly different from baseline (1.7 +/- 0.44 vs 1.4 +/- 0.52). At 52 weeks, steroid intake was reduced by 87 +/- 23% and 9 of the 13 patients no longer required corticosteroids. Moreover, both the clinical and functional scores were significantly better with respect to run-in values forced expiratory volume in one second (FEV1) 75 +/- 6 vs 60 +/- 10% predicted; forced vital capacity (FVC) 84 +/- 10 vs 77 +/- 13% pred; arterial oxygen tension (PaO2) 11.3 +/- 1.0 vs 10.7 +/- 1.3 kPa (84.5 +/- 7.8 vs 80.6 +/- 9.6 mmHg). No serious side-effects were recorded during the study; transaminase levels were increased in 62% of cases. In patients affected by chronic corticosteroid dependent asthma, the steroid-sparing effects of methotrexate and clinical improvement were apparent after 6 months treatment.