Indirect immunofluorescence was used to study the expression of desmosomal and intermediate filament (IF) proteins in the human notochord between the 4th and 12th weeks of embryonic development. Towards the end of this period, the development of the notochord is characterized by its gradual physiological atrophy and disappearance inside the vertebral bodies. In all of our embryos, the notochord cells expressed cytokeratin and vimentin but not desmin, neurofilament protein or glial fibrillary acidic protein. Throughout the stages studied, the expression of cytokeratin was strong. Vimentin expression, on the other hand, changed during the stages studied. In our youngest embryos, vimentin could be detected only in the peripheral cells of the notochord. During development, a distinct increase occurred in vimentin expression, and in the oldest embryos, all notochord cells showed bright vimentin-specific fluorescence. Simultaneously with this modification, a change occurred in the expression of desmosomal proteins: The notochord cells expressed desmoplakins abundantly during early stages, but weakly or not at all during later stages. Correspondingly, electron microscopy of the same stages showed a striking decrease in the number of desmosomes between notochord cells. Our results confirm that, during early development, the notochord displays features specific for epithelial cells. This accords with the view that notochord is of epithelial origin. The modifications observed in the expression of IF and desmosomal proteins were temporally correlated with developmentally regulated atrophy of the notochord. The programmed regression of the notochord cells is thus associated with a switch from a predominantly epithelial phenotype to a more mesenchymal one.