Lidocaine pharmacokinetics were studied in five fibrillated dogs undergoing external cardiopulmonary resuscitation (CPR) and five comparable control dogs. All animals were anesthetized with sodium pentobarbital and their electrocardiogram, arterial blood pressure, left ventricular pressure and carotid blood flow were monitored continuously. All dogs received a 2 mg/kg i.v. bolus dose of lidocaine. Multiple blood samples from venous, arterial, left ventricular and right atrial sites were obtained for determination of blood lidocaine concentration. At 60 min, the dogs were sacrificed. Lung, liver, kidney, brain, skeletal muscle and heart tissue samples were collected. There were dramatic differences between the control and CPR groups in arterial pressure, left ventricular pressure and carotid blood flow. In the CPR dogs, lidocaine blood concentrations for the entire 60 min were significantly higher than the control dogs and lidocaine clearance was reduced at least by 8-fold. A comparison of extraction ratios across skeletal muscle demonstrated that the phase of tissue uptake was prolonged in the CPR group. In each of the tissue samples, significantly higher tissue concentrations were observed in the CPR group. The results of our study show that lidocaine disposition is greatly altered during CPR and this is most likely due to a tremendous reduction of cardiac output and blood flow during CPR.