A battery of antibodies was used to assess development of the spinal cord and its neurons in mouse embryos with neural tube defects (NTDs). The two mutant strains examined, curly tail (ct) and splotch-delayed (Pax3Sp-d), develop an open neural tube for unrelated reasons, and thus provided for a complementary analysis. Five percent of embryos homozygous for the ct gene and 89% of embryos homozygous for the Pax3Sp-d gene develop spina bifida in the lumbosacral region of the neuraxis. Expression of several neuronal antigens, including Islet-1/2, polysialylated neural cell adhesion molecule (NCAM), neurofilaments, and a neuronal-specific nuclear protein (Neu-N) recognized by monoclonal antibody A60, were used as indicators of the level of differentiation of neuronal tissue. Immunohistochemical labeling suggests that early (embryonic days 12-15) neuronal differentiation in the dorsal and ventral region of the dysraphic neural tube occurs remarkably normally in both of the mutants. Similarly, labeling with antibodies to NCAM and neuroafilaments indicate that axonal development during early neurogenesis is unperturbed. Later stages of neuronal maturation, however, do not occur in the usual manner. Instead, the neuronal tissue begins a prodigious degeneration at embryonic day 17 (E17), so that by E18 only a rudimentary tissue remains. These results suggest that the aberrant morphology of the neural tube does not affect neuronal differentiation. However, the anomalous morphological and chemical environment may contribute to the neuronal degeneration observed at later stages.