Constant pressure perfusion of the sinus node artery in situ was performed in 9 dogs anesthetized with i. v. sodium pentobarbital, 30mg/kg. Sodium pentobarbital, 30μg to 10mg, was injected directly into the sinus node artery. Doses of more than 100μg of sodium pentobarbital usually induced a negative chronotropic response. The injection of more than 3mg of pentobarbital frequently caused sino-atrial block followed by AV nodal rhythm. Control sinus rhythm was restored within 5 minutes after pentobarbital injection. The pentobarbitalinduced bradycardia was not blocked by atropine or propranolol. The pentobarbital effect, 100μg to 3mg, was antagonized by norepinephrine, although a large amount of pentobarbital, 10mg, was not antagonized by large amounts of norepinephrine. When heart rate was accelerated by the continuous infusion of norepinephrine, the negative chronotropic pentobarbital effect was more readily induced. It is concluded that sodium pentobarbital directly depresses SA nodal pacemaker activity of the dog in situ and the depression is partially antagonized by norepinephrine.