Alemtuzumab is a humanized monoclonal antibody primarily used in refractory chronic lymphocytic leukemia. Although bronchospasm and infectious pneumonia are not uncommon adverse effects of therapy, alemtuzumab-associated interstitial pneumonitis causing acute respiratory failure has not yet been described. Here the authors describe a patient with chronic lymphocytic leukemia who developed acute respiratory failure following 3 weeks of alemtuzumab salvage therapy. A microbial or neoplastic cause of the lung disease could not be found. Findings of computed tomography of the chest and wedge biopsy were consistent with interstitial pneumonitis. The patient subsequently died of progressive respiratory failure after 2 months of hospitalization.