Psoriasis is a complex disorder involving alterations of many cell types. Although evidence suggests a T-cell pathogenesis for psoriasis, a primary role of T cells has not been directly demonstrated. Here, we show that reconstitution of scid/scid mice with minor histocompatibility mismatched naive CD4+ T lymphocytes resulted in skin alterations that strikingly resembled human psoriasis clinically, histopathologically and in cytokine expression. This skin disorder was diminished when memory T cells were coinjected. Thus, a subset of dysregulated CD4+ T cells can cause tissue alterations seen in psoriasis without the presence of CD8+ cells or a primary epithelial abnormality.