The effect of the Ca-chelators EDTA and EGTA on sinoatrial activity and heart irritability was studied in dog experiments by perfusing the artery supplying the sinoatrial node. Beside the usual ECG recordings left and right atrial and left and right ventricular epicardial electrograms, His-bundle electrogram and the early activity of the sinoatrial node were recorded. In addition action potentials were recorded from the left auricle and right ventricle of the dog hearts. Local application around the sinoatrial and atrio-ventricular nodes of EDTA and EGTA caused sinus bradycardia and later sinus arrest within 1 min after introduction of the drugs. For substitution of the sinus rhythm junctional (seldom lower atrial) escape rhythm developed. One to two minutes later it was followed by atrial premature beats and even later atrial flutter and fibrillation could be recorded. In one third of the cases atrial fibrillation was followed by secondary ventricular fibrillation. Atrio-ventricular impulse conduction was prolonged in the av node by EDTA and EGTA. Atrial action potentials and the slow (Ca dependent) ventricular action potentials were depressed by EDTA and EGTA.