Elevated levels of the serine proteinase plasminogen activator are observed in psoriatic lesions. In contrast to normal epidermis, lesional psoriatic epidermis contains primarily tissue type plasminogen activator (tPA) activity and much lower levels of urokinase type plasminogen activator (uPA) activity. Tissue plasminogen activator is also detectable immunocytochemically in lesional psoriatic but not normal epidermis. Similarly, mRNA for tPA is observed in lesional epidermis only. These results suggest that lesional psoriatic epidermis synthesizes enhanced levels of tPA compared to normal. Additional data support the hypothesis that enhanced tPA may be another marker common to psoriatic epidermis, epidermis during wound repair, and keratinocytes in culture. The significance of elevated tPA in psoriatic lesions is presently unclear, but its possible relationship to epidermal proliferation and cutaneous inflammation is under study.