The purpose of this study was to evaluate the efficacy and safety of low-dose weekly, oral methotrexate in patients with steroid-dependent or steroid-refractory inflammatory bowel disease (IBD). Oral methotrexate was given weekly at 15 mg/week. The primary criterion of response was based on steroid withdrawal. Of the 10 patients with Crohn's disease, daily prednisone dosage dropped from a mean of 37±9.6 mg to 8.3±2.1 mg/day (P<0.02); two had a complete withdrawal and four a partial response (<7.5 mg/day). In the eight patients with ulcerative colitis, daily prednisone dose dropped from a mean of 26.3±3.2 mg/day to 12.7±2.0 mg/day (P<0.001); three had a partial response. Adverse effects due to methotrexate were mild in both groups. We conclude that oral methotrexate may be useful and reasonably safe as a steroid-sparing agent in patients with refractory IBD. © 1993 Plenum Publishing Corporation.