Psoriasis is a hyperproliferative and inflammatory skin disorder of unknown aetiology. A fusion protein composed of human interleukin-2 and fragments of diphtheria toxin (DAB₃₈₉IL-2), which selectively blocks the growth of activated lymphocytes but not keratinocytes, was administered systemically to ten patients to gauge the contribution of activated T cells to the disease. Four patients showed striking clinical improvement and four moderate improvement, after two cycles of low dose IL-2–toxin. The reversal of several molecular markers of epidermal dysfunction was associated with a marked reduction in intraepidermal CD3⁺ and CD8⁺ T cells, suggesting a primary immunological basis for this widespread disorder.