The objective of this study was to determine long term efficacy and safety of low dose methotrexate (MTX) in treatment of rheumatoid arthritis (RA). Thirty patients receiving MTX for RA were prospectively studied over a mean treatment period of 60 months. Standard clinical and laboratory measures of disease activity were assessed by the same investigator at baseline, and at 3, 6, 24, and 60 months. The occurrence of adverse reactions was noted. Initially MTX was given orally 7.5 mg once a week. In the course of the observation the dose ranged between 5 and 15 mg/week. 13 patients (43%) completed 5-years study. Treatment with MTX was stopped due to adverse events in 4 cases, inefficacy in 7 patients, poor compliance and fear of toxicity in 3 patients and death in 3 patients. The factors related to their death were unrelated in all 3 cases to study MTX therapy. In 13 patients who completed 60 months of therapy, a significant improvement was noted comparing to baseline in 9 out of 12 clinical disease variables and acute phase reactants. There was also a significant decrease in the mean daily dosage of NSAIDs. Adverse events occurred in 64% of the patients, but only 13% of the patients discontinued MTX permanently. The side effects occurred more often in older patients. RA patients treated for five years with MTX showed statistically significant clinical improvement and decrease of inflammation parameters. MTX treatment may be helpful also in patients with advanced forms of RA.