Effect of propanidid on the pacemaker activity of the SA node was investigated in anesthetized dogs by injecting 30 microgram to 3 mg into the SA node artery in a single dose in a period of 4 sec. The doses of more than 100 microgram usually induced a negative chronotropic response. The injection of more than 1 mg frequently caused a sinus arrest followed by AV nodal rhythm. The initial sinus rhythm, however, was restored within 2 min after the propanidid administration. Its negative chronotropic response was not altered by pretreatment with atropine which completely blocked the action of acetylcholine. Bilateral vagotomy also did not affect the response induced by propanidid. A control solution or histamine failed to cause such a depressant effect on the SA node as observed after the propanidid injection. Thus, we conclude that propanidid supresses the SA nodal activity by a direct local action.