We evaluated the effects of methotrexate (MTX) on radiographic changes of rheumatoid arthritis (RA) in the hands, wrists, and feet of 31 patients who completed at least 24 months of treatment. Radiographs were obtained at baseline and every 1 or 2 years thereafter. MTX was administered for 2-6 years (mean 3.9 years); the total dose was 1,925 mg (range 970-3,810 mg). The mean duration of disease at baseline was 8.1 years (range 1-26 years). Radiographs taken over 1-5 years during previous, clinically ineffective, gold therapy (mean 2.2 years) were available for 24 patients, and the changes over time were compared. During MTX treatment, the mean number of swollen joints decreased from 22.5 to 8.3 (40 joints evaluated), and the mean erythrocyte sedimentation rate decreased from 61.6 mm/hour to 28.4 mm/hour. Thirty-six (19%) of 190 joints with Larsen scores of 0 at baseline progressed to a score of 1 or 2 within 1 year of beginning MTX, whereas with gold, 37 (44%) of 89 joints progressed (P less than 0.001). Of 419 joints with Larsen scores of 1, 12.5% deteriorated within 1 year with MTX treatment, compared with 14.7% of 183 joints during gold therapy (P not significant). There were no between-treatment differences for joints with higher Larsen scores. During gold therapy, the mean Larsen index (score per joint) for the hand and wrist joints (18 joints counted) progressed from 1.45 to 1.82 over a mean of 22.1 months, and during MTX, from 1.82 to 1.97 over a mean of 48.0 months.(ABSTRACT TRUNCATED AT 250 WORDS)