A stable junctional rhythm was produced in 16 dogs after surgical excision of the sinoatrial node and a large section of the crista terminalis. An unstable ectopic atrial rhythm appeared within the first week after surgery in 94% of the dogs. The pacemaker instability was characterized by spontaneous pacemaker shifts and periodic episodes of asystole which were prominent for several months after surgery in most of the dogs. In contrast to sinus arrhythmia observed before surgery, the ectopic atrial arrhythmias were not related to the respiratory cycle. The prompt disappearance of the asystoles after atropine or during treadmill exercise indicated the essential role of the vagus in producing the unstable rhythms. Atropine increased the average rate of the ectopic rhythms from 63 ± 3 beats/min to 107 ± 9 beats/min (p < 0.001) and shortened the corrected recovery time (CRT) following overdrive pacing from 3.8 ± 0.3 seconds to 1.9 ± 0.6 seconds (p < 0.001). Propranolol, in the absence of atropine, decreased the spontaneous heart rate from 56 ± 5 beats/min to 39 ± 6 beats/min (p < 0.01), and increased the CRT to 6.5 ± 2 seconds (p < 0.001) when administered after atropine. The data suggest that unstable ectopic atrial pacemakers could be responsible for ome of the arrhythmias associated with the sick sinus syndrome in man.