Development of the neural tube is often described as a continuous process that begins in the cervical region of the embryo and proceeds both rostrally and caudally. Examination of neural tube closure in the cranial region of LM/Bc and SWV/Bc mice revealed an intermittent pattern with four distinct areas of closure. Closure I begins at the level of somites 1–3 and proceeds bidirectionally. Closure II is initiated at the prosencephalic-mesencephalic border and also proceeds bidirectionally. Closure III is unidirectional, beginning adjacent to the stomodeum and proceeding caudally to meet closure II. Finally, closure IV takes place over the rhombencephalon where it meets closure II to complete rostral neural tube closure. In these two strains of mice anterior neural tube closure progressed as somite number increased. However, the SWV strain required a longer gestational time to develop equal numbers of somites and therefore to complete closure. In light of the intermittent pattern of closure observed in mice, the development of the rostral nervous system in other mammals, including humans, should be reconsidered. © 1993 Wiley-Liss, Inc.