Six mongrel dogs were used to investigate the mechanism of action of fentanyl-induced bradycardia. With controlled acid-base balance and temperature, and under 1.0 to 1.2 percent endtidal halothane anesthesia, 5 and microgram/kg of IV fentanyl citrate were given sequentially 1 hour apart and heart rate (HR) followed for 60 minutes. A dose-related depression of HR followed both injections. One week later the same dogs were studied similarly, except that bilateral cervical vagotomies were performed before fentanyl was given. The decrease in HR was at most 10 percent of the decrease in HR observed in the innervated dogs. Serum fentanyl levels were comparable. The data indicate the majority of the chronotropic action of fentanyl involves vagal efferent impulses from the central nervous system.