In this study, skin-infiltrating cells in psoriasis patients were characterized in biopsies from both involved and uninvolved skin. Histologic examination of biopsies showed the presence of both CD4+ and CD8+ T cells and the lack of B lymphocytes. Skin biopsies were also placed in tissue culture medium supplemented with human serum, interleukin-2 (IL-2), and irradiated autologous blood lymphocytes. T lymphocytes grew from both plaques and univolved skin biopsies and consisted of a heterogeneous population of T-cell subsets. The immunophenotypic analysis of cultured cells was comparable to the histologic examination on frozen section, i.e., there was a greater number of CD4/CDw29+ cells than CD8+/CD45+ cells. Cultures were tested in the primed lymphocyte test (PLT) and cell-mediated lympholysis (CML) assays. All cultures tested demonstrated secondary proliferative but not cytolytic reactivity. The PLT results indicate that the cell cultures generated are autoreactive. This autoreactivity was found to be directed against non-human leukocyte antigens (HLA), i.e., minor HLA with some restriction to major HLA antigens.