Psoriasis is a common T cell–mediated autoimmune inflammatory disease. We show that blocking the interaction of α₁β₁ integrin (VLA-1) with collagen prevented accumulation of epidermal T cells and immunopathology of psoriasis. α₁β₁ integrin, a major collagen-binding surface receptor, was exclusively expressed by epidermal but not dermal T cells. α₁β₁-positive T cells showed characteristic surface markers of effector memory cells and contained high levels of interferon-γ but not interleukin-4. Blockade of α₁β₁ inhibited migration of T cells into the epidermis in a clinically relevant xenotransplantation model. This was paralleled by a complete inhibition of psoriasis development, comparable to that caused by tumor necrosis factor-α blockers. These results define a crucial role for α₁β₁ in controlling the accumulation of epidermal type 1 polarized effector memory T cells in a common human immunopathology and provide the basis for new strategies in psoriasis treatment focusing on T cell–extracellular matrix interactions.