A 73-year-old female developed pulmonary disease during treatment with chlorambucil for polycythemia vera. Cough and dyspnea were prominent symptoms. A chest roentgenogram revealed interstitial fibrosis. The diffusing capacity was markedly reduced. Pathologic findings included alveolar lining cell dysplasia, interstitial round cell infiltrates and interstitial fibrosis. Resolution of the pulmonary symptoms and partial clearing of the fibrosis on chest roentgenogram followed discontinuation of the chlorambucil and institution of steroid treatment. Chlorambucil may cause pulmonary fibrosis similar to busulfan and cyclophosphamide and this may be a potential complication of all alkylating agents.