Methotrexate (MTX), which has been used for years in cancer treatment, is now being proposed as a first-line treatment for rheumatoid arthritis (RA), despite its potential side effects. The aim of this study was to investigate the short-term efficacy, safety and relative cost of low-dose MTX for the treatment of RA. We carried out an open, nonrandomized trial in which patients received a 7 mg injection of MTX once per week, with clinical and biological follow up. A single physician performed the weekly assessments, which involved evaluation of the duration of morning stiffness, the number of night awakenings, the number of painful and swollen joints and Ritchie's index. Blood cell count and erythrocyte sedimentation rate were determined monthly. Twelve RA patients were enrolled in the trial, over a mean treatment period of 356 +/- 175 days. A significant improvement was observed in all variables except the number of swollen joints. Ritchie's index decreased from a mean of 31.8 +/- 11.85 to 6.5 +/- 8.98 (p<1.6 x 10- 4). Minor adverse reactions were observed but none indicated treatment withdrawal: 6 cases of nausea, 2 of a moderate increase in transaminase activity, 1 of bronchitis, in which the responsibility of MTX was not definitely established and 3 cases in which hemoglobin levels decreased. The monthly cost of the treatment, including the drug itself and laboratory tests, is lower than that of gold salt injection. Three issues of key importance in our region were investigated in this study: 1) the possible desire to become pregnant of female patients undergoing MTX treatment. In addition, some of the young and unmarried patients did not understand or appreciate the contraceptive effects of the treatment; 2) poor compliance with the treatment due to limited financial resources. Many patients did not regularly attend for their follow-up appointments and many stopped taking the medication. One third of the patients were lost to follow-up during this study; 3) the prevalence of chronic hepatitis, which may limit the use of MTX in our region. Serological tests should be performed before the treatment is started and a liver biopsy is recommended for patients with chronic hepatitis B or C.