To investigate the contribution of cranial neural crest cells to the developing cardiovascular system in the chick embryo, cauterization of various regions of cranial neural crest was performed. Five regions may be distinguished, each of which contributes mesenchyme to pharyngeal (branchial) arches 1 through 4 and 6. Ablation of arch 3, 4, and 6 regions resulted in a high incidence of persistent truncus arteriosus (PTA) associated with anomalies of the aortic arch. Dextroposed aorta (DPA) or anomalies of the inflow tract were found in all ablation groups. Although anomalies of the aortic arch arteries were induced in all ablation groups and were usually associated with intracardiac anomalies, those of the third and right fourth aortic arch were most frequent in the arch 4 and arch 4 + 6 groups. Anomalies of the sixth aortic arch were most frequent after extensive ablations that included the arch 6 region. We speculate that PTA is a direct result of the decreased population of mesenchymal cells derived from the arch 3 through 6 neural crest regions. DPA or anomalies of the inflow tract may be related to altered hemodynamics due to anomalies induced by neural crest ablation. Anomalies of the aortic arch arteries may be caused by either the direct or indirect process. Circulation 75, No. 1, 255-264, 1987. IT HAS BEEN SHOWN in quail-chick chimeras that the cranial neural crest supplies ectomesenchymal cells to the pharyngeal arches, which contain the aortic arch arteries.1 Moreover, cranial neural crest cells extending from the auditory placode to somite 3 migrate to the outflow tract of the heart to participate in aorticopulmonary and truncal septation in the chick embryo.2 Surgical removal of these premigratory cells results in a high incidence of conotruncal anomalies, which include persistent truncus arteriosus (PTA) and doubleoutlet right ventricle (DORV)34 in combination with hypoplasia or absence of pharyngeal pouch derivatives, i.e., thymus and parathyroid glands.5 These anomalies induced by ablation of cranial neural crest have morphologic features that resemble those of the DiGeorge syndrome in man.DiGeorge syndrome in man is associated with interrupted aortic arch type B, PTA, and tetralogy of Fal-