Double-label immunohistochemistry was used to compare early aortic arch artery development in cardiac neural crest-ablated and sham-operated quail embryos ranging from stage 13 to stage 18. The monoclonal antibody QH-1 labeled endothelial cells and their precursors, and HNK-1 labeled migrating neural crest cells. In the sham-operated embryos, the third aortic arch artery developed from a lumenizing strand of endothelial precursors that became separated from the pharyngeal endoderm by migrating cardiac neural crest cells as they ensheathed the artery. The arch artery of the neural crest-ablated embryos lumenized but failed to become separated from the pharyngeal endoderm, indicating that neural crest is unnecessary for the early formation of the aortic arch artery. However, once blood flow was initiated through the third arch artery of crest-ablated embryos at stage 16, the artery became misshapen and sinusoidal. By embryonic day 3, abnormal connections to the dorsal aorta occurred and bilateral symmetry was lost, suggesting that the loss of neural crest-derived ectomesenchyme destabilizes the nascent artery. Although here we show no loss of the third arch artery, past studies have reported hypoplasia or missing carotids in older neural crest-ablated embryos (Bockman et al. [1987] Am. J. Anat. 180:332-341; Bockman et al. [1989] Anat. Rec. 225:209-217; Nishibatake et al. [1987] Circulation 75:255-264; Tomita et al. [1991] Circulation 84:1289-1295). We suggest that the cardiac neural crest is essential for the persistence of an arch artery, but not its formation. Furthermore, since changes in the development of the arch artery are seen prior to the formation of the tunica media, it is suggested that a critical period is reached in the development of the arch artery, after lumenization, but prior to the formation of the tunica media, which necessitates the presence of the cardiac neural crest.