If given in high doses, methotrexate (MTX), a folate antagonist, could cause pulmonary complications. To evaluate the pulmonary effects of low-dose methotrexate, 55 newly diagnosed patients with rheumatoid arthritis (RA) prescribed with MTX were studied prospectively. A significant reduction in percent predicted values of forced expiratory volume (FEV(1)), forced vital capacity (FVC), total lung capacity (TLC), and functional residual capacity (FRC) was observed after 2 years of MTX treatment. A significant increase in the FEV(1):FVC ratio was also observed. In comparison to the normal annual decline in healthy adults, the actual reduction in observed values in the patients was significantly greater (3.2, 6.3, and 6.7 times normal for FEV(1), FVC, and TLC, respectively). PaO(2) and oxygen saturation showed marginal but significant improvement. It was concluded that low-dose MTX treatment in RA might cause an accelerated decline in lung function. Therefore, periodic monitoring of pulmonary function among RA patients started on MTX could be necessary.