To determine the electrophysiological effects of propofol and to explain the potential mechanism(s) whereby it causes bradyarrhythmias, 10 closed-chest pigs weighing 20-25 kg were studied. Each animal was premedicated by intramuscular administration of ketamine hydrochloride, intubated, and mechanically ventilated. Femoral arterial and venous catheters were placed, and a comprehensive electrophysiologic evaluation was performed at baseline and after two doses (1 mg/kg i.v. bolus and 0.1 mg/kg/min infusion and an extra 1-mg/kg i.v. bolus and 0.2 mg/kg/min infusion) of propofol. The electrophysiological effects obtained on low- and high-dose propofol were compared to baseline values. Propofol caused a dose-related decrease in sinus cycle length (baseline 565 ± 36 ms, low-dose propofol 541 ± 28, high-dose propofol 527 ± 26 ms; p < 0.05), a prolongation of the corrected sinus node recovery time (baseline 119 ± 35 ms, low-dose propofol 126 ± 32, high-dose propofol 130 ± 30 ms; p < 0.01), and an increase in the His-ventricular interval (baseline 33 ± 4 ms, low-dose propofol 36 ± 4, high-dose propofol 40 ± 3 ms; p < 0.005). All other electrophysiological parameters remained unchanged, and there were no cases of spontaneous atrioventricular block or sinus pauses. We conclude that propofol causes dose-related depression of sinus node and His-Purkinje system functions, but has no effect on the atrioventricular node function and on the conduction properties of atrial and ventricular tissues in normal pig hearts.