Twenty-three patients were included in this prospective study about the safety and efficacy of oral low dose methotrexate (MTX) in the treatment of refractory rheumatoid arthritis. Patients received a mean dosage of 6.6 +/- 1.8 (SD) mg weekly over a mean duration of 16.6 +/- 12.5 months. Patients improved significantly in all clinical parameters of efficacy. There were significant reductions in Lansbury joint scores (p less than 0.001), duration of morning stiffness (p less than 0.001), sedimentation rates (p less than 0.001), C-reactive protein (p less than 0.01), IgG(p less than 0.01), rheumatoid factor (p less than 0.01) and significant increase in grip strength (p less than 0.001), hemoglobin (p less than 0.05) after 17 months of treatment with MTX. Radiographic progression of joint disease were assessed using global scoring method. The mean rate of development of erosions and joint-space narrowing during MTX therapy was significantly less than the rate of radiographic progression before MTX therapy (8.1 +/- 7. 9/year vs. 1.9 +/- 3.8; p less than 0.05). Adverse reactions during MTX therapy included transient transaminase elevation (17.4%). Five patients (21.7%) were withdrawn because of leukopenia (2), interstitial pneumonitis (1), stomatitis (1), skin rash (1). We conclude that low-dose methotrexate is effective for the management of clinical disease activity in patients with refractory rheumatoid arthritis and may be a disease-modifying anti-rheumatic drugs (DMAR-Ds) by roentgenographic criteria.