We investigated 43 patients with seropositive rheumatoid arthritis (RA) under a therapy with methotrexate (MTX) or azathioprine (AZA). All patients fulfilled the American Rheumatism Association criteria. It has been a retrospective study over 2.6 years (MTX: 26 patients, average age 54 +/- 14.6 years, female/male 19:7, AZA: 17 patients, average age 59.4 +/- 12.5 years, female/male 12:5). The mean duration of disease was 8 years (+/- 5.3) in the MTX-group and 7 years (+/- 7.3) in the AZA-group. The mean dose of MTX was 13. 3mg/week and of azathioprine 142.6mg/ daily. The drugs were administered orally. - Radiographs of hands, wrists and feet obtained at enrollment and at review were scored by a rheumatologist according to a modified Larsen score. Radiographic damages were counted in 25 joints of each hand and in 25 joints of each foot. The change in radiological score was calculated by subtracting the joint damage scores at follow up with first damage score at inclusion. The rate of radiological progression (YP) was calculated by dividing the change in radiological score by the number of years during the period of study. - Only 3 patients with MTX showed no radiologic progression. All other patients of both groups showed progressive radiological changes. - The study demonstrated no significant difference in the rate of radiologic progression between the different treatment-groups. However, there was a trend that MTX treated patients (YP 5 +/- 4.4) had a slower radiographic progression compared with those treated with AZA (YP 8.5 +/- 7.7). MTX may be more effective in patients at an earlier stage of rheumatoid arthritis. - When we started a therapy with AZA or MTX in a later period of disease we revealed a better influence of radiologic progression under AZA and a trend towards an increase of the radiologic progression under MTX. - Probably there is a decreasing effect of MTX in later periods of the disease. - The corticoid dose reduction was higher under AZA (AZA: Reduction about 58.6%, MTX: 25%) over the study duration. - Our investigation demonstrated a trend towards reduced radiological progression in MTX treated patients compared to AZA, however statistic analysis showed no significant difference in the rate of radiologic progression. At an earlier stage of the disease there is a better influence of MTX in radiologic progression, at the later stage we showed a slowing of radiological deterioration in AZA treated group.