Treatment with methotrexate (MTX) in rheumatoid arthritis (RA) can lead to severe side-effects, especially pulmonary and haematological complications. The aim of this retrospective study was to evaluate, during a 6 yr period, the prevalence and severity of bronchopulmonary side-effects in RA patients treated with MTX. A cohort of 130 RA in-patients (106 women, 24 men) treated with MTX was studied for the occurrence of respiratory adverse events. Adverse bronchopulmonary side-effects were observed in 12 patients (two men, 10 women), with a mean disease duration of 15 yr. Only three patients had previously suffered from pulmonary disease. MTX treatment duration was between 1 month and 4.5 yr. The diagnosis was that of hypersensitivity pneumonitis (HSP) in four cases, non-HSP pneumonitis in five patients with one case of Pneumocystis carinii infection, and bronchitis in three cases. The initial respiratory symptoms were not discriminatory between the different conditions. Risk factors were not identified for the occurrence of HSP. HSP always occurred in the first 5 months of treatment. Two patients with HSP died, and another patient with opportunistic infection underwent tracheostomy. HSP represents a potentially lethal side-effect in RA patients treated with MTX. Improved education of patients and physicians should certainly lead to a reduction of both the prevalence and severity of pulmonary side-effects during MTX therapy in RA.