With the purpose of studying the interactions between sino-atrial (S-A) node and His bundle escape rhythms (HBER), negative chronotropic agents (verapamil, manganese and droperidol) were directly injected in the canine S-A node through its cannulated and autoperfused artery. HBER followed S-A node depression assessed by His bundle electrograms. A well established correlation was found between HBER and S-A node initial rate. His bundle recovery time following an atrial overdrive was 50 times larger than the S-A node recovery time. HBER was found to be more sensitive to sympathetic blockade than to vagal influences. It is concluded that 1) recovery time following overdrive stimulation is a valid index reflecting sinus nodal function; 2) HBER commonly results from selective depression of the S-A node not only depends on rate but also on overdrive suppression; 4) HBER is more sensitive to sympatheticmodulation.