Invasive pulmonary aspergillosis is a well-recognized complication in immunocompromised patients, especially those with neutropenia. We report four cases of invasive pulmonary aspergillosis in patients whose main underlying disease was chronic obstructive pulmonary disease (COPD). Two patients had an acute fatal course, one had chronic necrotizing pulmonary aspergillosis ending in an acute fatal course, and the other had a semiacute disease that responded to amphotericin B. Autopsy on three patients showed invasive pulmonary aspergillosis in both lungs, and tissue invasion was documented by transbronchial biopsy in the patient who survived. Retrospective review of all cultures that grew Aspergillus species from bronchoscopic specimens showed no false-positive results, and this procedure proved to be the most useful maneuver in making the diagnosis. Invasive pulmonary aspergillosis should be in the differential diagnosis in patients with COPD and unexplained pulmonary infiltrates.