To analyze the possible adverse effects of low dose methotrexate (MTX) therapy, 276 patients with rheumatoid arthritis (RA) were examined retrospectively. One hundred and seven patients (39%) experienced 113 adverse events : 57 showed liver dysfunction, 24 gastrointestinal complaints, 13 cutaneous symptoms, 6 respiratory symptoms, and 6 malignancies. Interestingly, 3 patients developed a dry cough without infiltration nor interstitial shadow on chest X-ray. The cough was rapidly resolved by discontinuation of MTX, but it recurred in 1 patient when MTX was re-administered. This finding might suggest a close association between MTX administration and the occurrence of dry cough. Of the 6 patients with malignancies diagnosed during MTX therapy, 2 showed malignant lymphoma, 2 lung cancer, 1 breast cancer and 1 colon cancer. MTX might have an oncogenic potential in RA because the coincidence rate, especially with respect to lymphoma, was significantly higher than estimated in a normal population.