A 64-year-old man was admitted to our hospital complaining of dyspnea and fever. He had been treated with low-dose methotrexate for rheumatoid arthritis. Chest radiography showed diffuse ground-glass attenuation in both lung fields, and hypoxia was detected. Pneumosystis carinii pneumonia was demonstrated on transbronchial lung biopsy, and the serum beta-D glucan level was high. We started treatment with trimethoprim-sulphamethoxazole, but respiratory failure worsened, and drug-induced pancytopenia occurred. Although trimethoprim-sulphamethoxazole was stopped, pancytopenia persisted and the patient required ventilatory support. After we changed the medication from trimethoprim-sulphamethoxazole to pentamidine, respiratory failure improved. It was thought that pneumocystis carinii pneumonia was associated with low-dose methotrexate and that trimethoprim-sulphamethoxazole interacted with methotrexate to induce severe pancytopenia.