BACKGROUND--The location of the sinus node is known to be at best abnormal, or at worst unknown, in patients with isomerism of the morphologically left atrial appendage. In contrast, the sinus node is known to be an excellent histological marker of the morphologically right appendage, being duplicated in those with right isomerism. The aim of the study was to investigate this condition further in fetal human and mouse hearts. METHODS--Serial histological sections of the area anticipated to contain the sinus node were studied in hearts with isomerism of the atrial appendages taken from 14 human fetuses and 13 iv/iv mice, using 12 mouse hearts with normally arranged or mirror imaged atrial chambers for controls. RESULTS--All hearts with isomerism of the right appendages (two human and four mouse) had bilateral sinus nodes. The cases with isomerism of the left appendages (12 human and nine mouse) showed absence of a recognisable sinus node except in four cases (19%) in which a small remnant of the node was found. In three of these cases, it was related postero-inferiorly to the superior cavoatrial junction. CONCLUSIONS--The concept of isomerism of the atrial appendages is endorsed by findings on the morphology of the sinus node, this being the most reliable histological criterion for existence of a morphologically right atrium. A small proportion of hearts with left isomerism had a structure resembling the sinus node, but it was hypoplastic and displaced postero-inferiorly, distant from its expected position had the hearts possessed an incompletely formed morphologically right appendage.