Baseline and sequential liver biopsies were performed in ten patients with rheumatoid arthritis (RA) treated with methotrexate (MTX) for more than 4 years. Liver biopsies were performed in all patients before the initiation of MTX therapy and were repeated after reaching a cumulative dose of 1500 mg or more. In four patients a third biopsy was performed 3 years after the first one. No significant worsening of hepatic architecture was found in any of our patients after 4 to 7 1/2 years of MTX therapy. No correlations between histologic findings and various clinical or pharmacological variables could be found. Our results suggested that prolonged MTX administration in RA patients did not cause severe hepatic abnormalities.