Epidermal keratinocytes separated from skin lesions of non‐bullous congenital ichthyosiform erythroderma were investigated in an attempt at experimental reproduction of this keratinization disorder.In vitrostudies on growth and differentiation of pathological keratinocytes isolated from the influence of the host's dermal and humoral components were performed using the immersed epidermal cell culture technique. Ten to 25‐ day‐old confluent and stratified cultures were examined by means of photonic and electron microscopy, and stained with various differentiation markers for indirect immunofluorescence studies. The cultured epidermis showed low‐grade differentiation and no clear‐cut evenly distributed signs of the original disease. Grafting on congenitally athymic nude mice allowed further differentiation of the epidermal sheets and re‐expression of the histologic and ultrastructural features of non‐bullous congenital ichthyosiform erythroderma. Thus, the purely epidermal origin of this particular form of autosomal recessive ichthyosis could be confirmed. Large amounts of pathological keratinocytes generated from small skin biopsies may be used for experimental purposes after grafting on several at