Objective: To report a case of acute respiratory failure after a single dose of quetiapine fumarate in an elderly patient with a history of chronic obstructive pulmonary disease (COPD). Case Summary: A 92-year-old woman with a history of COPD was admitted to the hospital with pneumonia. Her symptoms improved with antibiotics. Because of acute agitation and delirium, quetiapine 50 mg twice daily was started. After receiving the first dose, the woman developed acute respiratory failure and severe central nervous system depression. She required mechanical ventilation and supportive care in the intensive care unit (ICU). She had a full recovery within 24 hours. Discussion: Quetiapine is an atypical antipsychotic that has been used successfully for the treatment of schizophrenia and bipolar disorder for many years. Recently, it has also been used to treat delirium and agitation. It has proven to be very safe, even in the elderly. In previously reported cases, serious adverse effects were seen in patients who ingested very high doses of quetiapine. Those patients required intubation and supportive care in the ICU. To our knowledge, as of January 19, 2006, this is the first case report of acute respiratory failure of such severity with one dose of quetiapine. Using the Naranjo probability scale, we conclude that the acute respiratory failure observed in this patient was probably related to quetiapine. Conclusions: This case suggests that quetiapine can have significant adverse effects even with a single 50 mg dose. Elderly patients, especially those with significant underlying pulmonary pathology, should be monitored closely when started on this medication.