One hundred and thirty seven rheumatoid arthritis (RA) patients refractory to D-penicillamine and some of them (15%) refractory to other slow active drugs were treated with oral methotrexate (MTX) (10-15 mg weekly). After 12-24 months of treatment, 94 and 74 patients respectively showed a significant improvement as judged by duration of morning stiffness (p less than 0.0001), grip strength (p less than 0.0001), degree of joint swelling (p less than 0.01) and tenderness (p less than 0.0001) compared to pre-treatment values. This clinical improvement was also associated with a decrease of erythrocyte sedimentation rate (p less than 0.001), decrease of C-reactive protein (p less than 0.0001) and with improvement of anaemia (p less than 0.05). No changes were seen in rheumatoid factor titres. Seventy-four of the patients were followed for up to 24 months. Thirty-one of them (23%) had complete remission and 43 (31%) had an excellent response. Adverse drug reaction during MTX therapy included: elevated liver enzymes in 34 patients, mucosal ulcers in 21, nausea and vomiting in 8, diarrhoea in 4, leukopenia in 2, interstitial pneumonitis in one, intestinal bleeding in one and finally septic arthritis in another patient. The majority of these side effects were resolved without sequelae. However, 15 patients (11%) with adverse drug reactions had to discontinue the treatment. Forty-one of our patients who received a cumulative mean dose of MTX of 1550.5 +/- 235.5 mg underwent a percutaneous liver biopsy. Ten patients had normal tissue, 12 had minimal changes, 13 nonspecific changes and 6 patients had mild fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)