A systematic analysis of the efficacy of methotrexate (MTX) in severe rheumatoid arthritis (RA) was carried out. Twenty-one patients with severe classical RA resistant to conventional therapy were treated with 7.5 to 25 mg of oral or intramuscular MTX for 3-114 weeks (mean of 38 weeks). Eleven patients (52.4%) showed definite clinical improvement and a fall in sedimentation rate; some improvement was seen in 5 other patients (23.8%). Two patients were unresponsive. Three patients discontinued MTX, 1 because of acute hepatitis and the other 2 because of noncompliance and fear of toxicity. Abnormal liver function tests reversible with modification of therapy occurred frequently. Other side effects were minor. The results of this uncontrolled study indicate that MTX may be an effective drug for the treatment of severe RA. Double blind trials and longterm followup are needed prior to its widespread use in RA.