Pulmonary toxicity occurs after the administration of several different chemotherapeutic agents. Pulmonary toxicity due to melphalan alone has not been documented. In the patient we describe respiratory symptoms and pulmonary infiltrates developed twice within two weeks of the second course of a monthly melphalan and prednisone regimen. Open lung biopsy revealed interstitial pneumonitis. The infiltrates cleared on both occasions when melphalan was withheld. Special studies performed seven weeks after the last dose of melphalan had been given revealed that the patient's alveolar macrophages suppressed phytohemagglutinin induced blastogenesis of his peripheral lymphocytes. Melphalan itself did not stimulate the blastogenesis of the peripheral lymphocytes. Melphalan should be added to the list of therapeutic agents that induce pulmonary disease. However, the pathogenesis of the disease remains to be elucidated.