Whole-skin grafts from a patient with lamellar ichthyosis were maintained on athymic nude mice for periods of 6 weeks to 4 months with excellent preservation of all gross and histologic features of the disease. In recombinant grafts composed of lamellar ichthyosis epidermis and normal dermis grown for periods up to 87 days on nude mice, the abnormal epidermis retained all the features of lamellar ichthyosis. Similar results were found in recombinants of lamellar ichthyosis epidermis and dermis. In recombinant grafts of normal epidermis and lamellar ichthyosis dermis, the epidermis remained normal and did not become ichthyotic. These observations support the hypothesis that the defective gene in lamellar ichthyosis acts directly on the epidermis as opposed to acting indirectly through a systemic abnormality or through an effect on neighboring dermis.