BACKGROUND: Mouse fetuses with spontaneous myelomeningocele (MMC) were investigated, determining the various levels of dysraphism in soft tissue, spinal cord, and vertebrae. Morphology was correlated with hind limb function. METHODS: Viable curly tail/loop tail mouse fetuses underwent qualitative standardized ex utero examination of tail and hind limb sensitivity and motor response. Afterward, they were processed either for histology or skeletal preparation. RESULTS: All animals displayed identical cranial levels of soft tissue and neural defects. The cranial opening of the vertebral defects were invariably located more cranially (range, 0.5-5 vertebrae; mean = 2.25). The caudal opening of soft/neural tissue and bony defects was invariably at the coccygeal base. The comparison of functional with morphological levels demonstrated that, in 52.5%, the level of the soft/neural tissue dysraphism and, in 47.5%, the level of the bony opening correlated with the neurologic deficit. CONCLUSION: The naturally occurring soft tissue coverage over the MMC could exert a protective effect toward the underlying spinal cord. This interpretation supports the concept that in utero acquired destruction of exposed neural tissue is a main factor for the neonatal functional deficit. Thus, these data are consistent with the rationale for prenatal MMC repair in humans.