We undertook a retrospective review of all the liver biopsies done by us between 1985 and 1990 for the purpose of monitoring methotrexate (MTX)-induced hepatotoxicity in rheumatoid arthritis (RA) patients. A total of 29 biopsies were done in 25 patients. The mean total cumulative dose of MTX was 1585 +/- 348 (SD) mg. Average duration of MTX therapy was 31 +/- 9.8 mo (SD). Liver biopsy after accumulating 900 mg and 1200 mg MTX, respectively, in 2 obese diabetic patients showed evidence of cirrhosis. Obese diabetics may represent a subgroup of RA patients at risk for developing MTX-induced hepatotoxicity.