A recent study in human fetuses with myelomeningocele (MMC) suggested that the primary malformation is not neural but a failed closure of the posterior vertebral column and paraspinal soft tissue, which leads to exposure and secondary destruction of the spinal cord. The goal of this study was to test whether chronic exposure of the normal spinal cord to the amniotic space produces a lesion similar to human MMC. In fetal sheep at 75 days' gestation (group A) and 60 days' gestation (group B) (term = 150 days), the lumbar spinal cord was exposed to the amniotic cavity by excising skin and paraspinal soft tissues, and by performing a laminectomy. Some animals from both groups were fetectomized and assessed morphologically at 100 days' gestation. The remainder were delivered near term and assessed clinically, electrophysiologically, and morphologically. In group A, all animals showed MMC-type pathology. The exposed spinal cord was herniated out of the spinal canal and rested on the dorsal membranes of a cystic sac. The neural tissue was stretched and flattened out. Histologically, the hallmarks of the spinal cord were not discernable and the cytoarchitecture was lost. These changes were less severe at 100 days than at term. The three survivors in group A were paraplegic. In group B, the two survivors and two fetuses harvested at 100 days had healed skin wounds and near normal spinal cord histology. The other animal harvested at 100 days had a MMC-type lesion with less severe histological changes. The two survivors had a mild paraparesis.(ABSTRACT TRUNCATED AT 250 WORDS)