BACKGROUND: We observed fentanyl known as centrally-acting antitussive agents provoke a cough response in some patients at induction of anesthesia. This may be of clinical importance. METHOD: 121 patients (ASA class I) were assigned randomly to 4 groups. Each group was given different doses of fentanyll Group 1 (n=30); 0.5ug/kg, Group 2 (n=30); 1ug/kg, Group 3 (n=33); 2ug/kg, Group 4 (n=28); 4 g/kgl, within 1 second through a peripheral venous cannula before induction of anesthesia. All patients were observed carefully in order to detect a cough response and any side effects. RESULT: The incidences of FCR (Fentanyl Cough Response) were 0% in Group 1, 10.0% in Group 2, 30.3% in Group 3, and 39.3% in Group 4. The ED50 of FCR was 4.25ug/kg. The mean onset-time from the end of fentanyl administration to the beginning of coughing was 12.5 seconds. FCR was decreased with aging, but not affected by weight, height, or smoking. Other serious side effects were not accompanied. CONCLUSION: Fentanyl can evoke the pulmonary chemoreflex dose-dependently and the ED50 was 4.25 g/kg.