Abstract The segregation of neural crest cells from the neural folds and their early migration along three cranial pathways in the avian embryo have been described on the ultrastructural level. Major findings are the following: First, before neural crest segregation, the basal lamina underlying the neural folds undergoes temporal changes in distribution that correlate with alterations in tissue geometry. Second, although the neural tube always becomes continuous at its lumenal surface as crest cells segregate, the time at which ectoderm fuses across the midline bears no constant temporal relationship to crest segregation. Third, a ridge on the dorsolateral neuroepithelium may inhibit ventral movement of crest cells in the mesencephalon. Fourth, cranial crest cells orient toward surfaces with an abundant extracellular matrix or basal lamina. Mesodermal cells do not appear to serve as substrata for migration. Fifth, interstitial bodies are more prominent along the pathways of migration than elsewhere in the embryo. Sixth, the direction of orientation of matrix fibers along anterior crest pathways is normal to the direction of migration of crest cells and appears not to guide migration.