Research into the cause and pathophysiological mechanisms underlying expression of psoriatric skin lesions has been hampered by lack of an appropriate animal model for this common and enigmatic cutaneous disease. These studies characterize normal skin, pre-psoriatic skin, and psoriatic plaque skin samples transplanted onto severe combined immunodeficiency mice. In this report we document that 1), normal, prepsoriatic, and psoriatic plaque keratome skin samples can be transplanted onto severe combined immunodeficiency mice reliably with high rates of graft survival (> 85%) and with reproducible changes consistently observed over prolonged periods of engraftment; 2), after transplantation, by clinical assessment and routine light microscopy, normal skin remained essentially normal whereas pre-psoriatic skin became thicker, and psoriatic plaque skin retained its characteristic plaque-type elevation and scale; 3), by using a panel of antibodies and immunohistochemical analysis, the overall phenotype of human cell types (including immunocytes) that persisted in the transplanted skin was remarkably similar to the immunophenotype of pretransplanted skin samples; 4), clearly recognized interface zones between human and murine skin within the epidermal and dermal compartments could be identified by routine microscopy and immunostaining, with focal areas of chimerism; and 5), elevated interleukin 8 cytokine levels were present in transplanted pre-psoriatic and psoriatic plaque skin samples. We conclude that there are many similarities between pre- and post-transplanted human samples of normal and psoriatic skin that are grafted onto severe combined immunodeficiency mice. Thus, we propose that this new animal model is appropriate for additional mechanistic-type studies designed to reveal the underlying genetic/etiological abnormality, as well as better illuminate the pathophysiological basis, for this important skin disease.