Palatal histogenesis in hydrocortisone-treated hamster fetuses was studied by both light and electron microscopy. At an early stage in the hydrocortisone-affected fetuses, when the palatal shelves hung vertically on either side of the tongue, necortic changes could be seen in some of the basal epithelial cells which lay adjacent to the fragmented basal lamina. The normal looking cells lay on an intact basal lamina and were attached to the contiguous necrotic cells by desmosomes. With horizontal reorientation of the palatal shelves and their approach to the midline, cellular necrosis and fragmentation of the basal lamina increased. When compared with normal cells, the hydrocortisone-affected ones were seen to be lighter, to contain fewer ribosomes and no lysosomes. At a later stage, when midline palatal fusion was lacking, the epithelium underwent stratification and keratinization while the necrotic debris was removed by mesenchymal macrophages. It appears that the normal process of protein synthesis is inhibited following hydrocortisone administration and that this, in turn, during palatogenesis, disrupts normal cellular differentiation and the integrity of the basal lamina, which are associated with the production of a cleft palate.