Cells from the cardiac neural crest are essential for the normal development of both the heart and the great vessels. If cardiac neural crest is ablated surgically from Hamburger-Hamilton stage 9 chicken embryos, they will develop anomalies of both the heart and great vessels that are similar to anomalies that occur in humans. In the absence of cardiac neural crest, another area of neural ectoderm (nodose placode) provides replacement cells that are less competent than those of the neural crest. In this study, both the cardiac neural crest and the nodose placodes have been surgically ablated. A syndrome of unusual prevalence (47%) and severity was found among the survivors of this surgery, which was characterized by a large undivided aorta that arched dorsally without right or left deviation to become the dorsal aorta. There was no other tributary to the formation of the dorsal aorta. There were no ducti arteriosi, and the pulmonary arteries were both ectopic and hypoplastic. The brachiocephalic arteries were asymmetric and hypoplastic. The association of the aorta with the anlagen of the thyroid and thymus glands, as well as with the inferior ganglion of the vagus nerve, indicated that the solitary surviving aortic arch artery is that of arch III in this syndrome. These results establish a biological limit of the plasticity of the neural ectoderm and give a probable cellular basis for a lethal congenital septal defect.