Methotrexate is an antimetabolite commonly used in clinical practice for a variety of indications ranging from rheumatoid arthritis and other connective tissue disorders to high dose regimens in many malignancies. This folate antagonist has got a spectrum of toxicities among which gastrointestinal effects predominate. Lung injury is a well described but rare event and has been reported most often in patients who have been on long term oral therapy for rheumatic disorders. Acute lung injury in a patient receiving a high dose regimen for haematological malignancies has not been reported previously. We present one such case of methotrexate related acute lung injury in a patient of primary CNS lymphoma receiving high dose methotrexate.