We investigated the epidermal ultrastructure of an organotypic skin culture model over a culture period of one week. At delivery, the stratified keratinizing epidermis consists of a basal layer with hemidesmosomes, a spinous layer with desmosomes, a granular layer with keratohyalin and membrane coating granules, a horny layer enclosing many lipid droplets. At the epidermal-dermal junction laminae lucida and densa are evident. After 7 days of culture the multilayered cornifying aspect persists; the number of viable cell layers remains constant. Spinous cells display abundant glycogen deposits. In the granular layer keratohyalin granules are more abundant. Both the size and number of hemidesmosomes increase. Anchoring fibrils are observed. From a structural point of view the model remains stable and well differentiated in culture and, therefore, may be well suited for pharmacological purposes.