Flaky skin (fsn) is an autosomal recessive mouse mutation with papulosquamous disease features similar to human psoriasis. In fsn/fsn skin, one sees marked acanthosis and hyperkeratosis with focal parakeratosis, subcorneal pustules, dermal capillary dilation, and a marked diffuse dermal infiltration of mixed inflammatory cells, predominantly lymphocytes. To determine if these pathologic features are a characteristic of the skin or a chronic autoimmune attack, we placed full-thickness skin grafts from affected homozygous (fsn/fsn) and normal littermate control (+/?) mice on the dorsal skin of genetically athymic nude (nu/nu) mice. After 10 weeks of observation, the grafts maintained the histologic phenotype of the donor animal. In the fsn/fsn grafts, there was persistence of both epidermal proliferation and dermal inflammation, characteristics of the mutation. The fsn/fsn phenotype was also confirmed by immunohistochemical evaluation for specific mouse keratinocyte marker expression. Based on tritiated thymidine uptake, we found DNA synthesis rates elevated threefold or more in fsn/fsn epidermis compared to littermate control mouse skin. Elevated rates of DNA synthesis remained a feature of the fsn/fsn grafts but not that of littermate control skin grafts. This study demonstrates that the psoriasiform phenotype of this mouse mutation can persist independent of the host thymic-derived immune system.