BACKGROUND--The sinus node is known to be duplicated in hearts with bilateral right appendages, but its site is uncertain when both appendages are of morphologically left pattern. OBJECTIVE--To determine the earliest site of activation of the atria, and to assess this site of activation relative to the anticipated location of the sinus node in patients with isomeric atrial appendages. STUDY DESIGN--Electrophysiological recordings by epicardial mapping during operations through a median sternotomy. PATIENTS--Since 1987, 44 consecutive patients with isomeric right appendages and 23 with isomeric left appendages. RESULTS--In 77% of the patients with isomeric right appendages, the site of earliest activation was superiorly located at the junction of one or other atrium and a superior caval vein; in other words, in the anticipated site of a sinus node. In contrast, an inferior site of earliest activation at the junction of an atrium with an hepatic vein was most common in patients with isomeric left appendages (56%). The site of earliest activation was not related to the veno-atrial junctions in six patients with isomeric right appendages (14%), nor in five with isomeric left appendages (22%). Moreover, in six patients with isomeric right appendages (13%), and three with isomeric left appendages (13%), additional sites of earliest activation were observed when the dominant site was suppressed. The locations of the earliest activation observed by epicardial mapping did not always accord with those expected from the preoperative electrophysiological examination, nor did they always match the anticipated site of the sinus node as documented by previous histological investigations. CONCLUSIONS--Epicardial mapping showed marked variation in functional arrangement of the earliest atrial activation. This information could be of future use when planning surgical procedures.