Pulmonary hemorrhage is a rare cause of death in patients with acute leukemia. Within a 3-month period we observed three such cases, all of which were associated with the gram-negative opportunistic pathogen Stenotrophomonas maltophilia. Since fatal lung bleeding had previously not been observed in conjunction with this organism, we collected the data from all patients with documented S. maltophilia infections or colonizations of the past year and analyzed the risk factors for a lethal outcome. A total of eight patients were identified. In the three patients with fatal hemorrhage, the interval between first complaints (chest pain, cough, fever) and death from lung bleeding was 36-72 h. A fourth patient with acute leukemia died of nonhemorrhagic respiratory failure 9 days after developing S. maltophilia-associated pneumonia. All four patients had received intensive chemotherapy and were severely neutropenic and thrombocytopenic. Such a combination of predisposing factors was not observed in the four patients with nonfatal infections or colonizations. Pulsed-field gel electrophoresis demonstrated that the infections were unrelated. S. maltophilia was also isolated from a faucet in a patient's room, but the strain isolated was genetically different from the strain causing the patient's pneumonia. Our data suggest that severe bone marrow aplasia and a recent history of intensive chemotherapy are predisposing factors for the development of fulminant hemorrhagic S. maltophilia pneumonia. Since some of the infections and colonizations developed despite prophylactic administration of antibacterial agents with documented in vitro activity against the pathogen and none was controlled by such agents, it is clear an efficient treatment strategy needs to be developed.