An ultrastructural study of the heart of the tsetse fly, Glossina morsitans, and of several other species of cyclorraphan flies revealed that the ventral region of the heart of adult flies is supported by a muscular septum not present in the larval stage. The pericardial septum of the adult heart is composed laterally of alary muscles and a central longitudinal muscle that extends the length of the abdominal aorta, whereas the larval heart is supported ventrally only by alary muscles and strands of connective tissue. Thus, unlike the larval stage, and the heart of other insects, the pericardial septum of adult cyclorraphan flies contains a central band of longitudinal muscle, that along with the alary muscle, forms a large pericardial sinus lying between the septum and the heart. Neurosecretory nerves arising from the lateral nerves of the thoracicoabdominal ganglion extend dorsad to the pericardial septum, where they form neuromuscular junctions on the muscle fibers of the pericardial septum or traverse the septum terminating in the pericardial sinus, thereby creating one of the largest neurohemal organs in these flies. In the tsetse fly, some of the neurosecretory fibers also extend between the muscle fibers of the myocardium, and release their material into the lumen of the heart.