Various human malignant tumors including malignant melanoma showed an absence of fibrinolytic activity in previous histochemical fibrin studies. In contrast, a tissue plasminogen activator has been isolated both from extracts of melanoma tissues and melanoma cell lines in culture and has been characterized to be a potent plasminogen activator. In an attempt to resolve this apparent discrepancy, we studied biopsies specimens of melanoma, several melanoma cell lines and melanoma xenografts by the immunoperoxidase method. Tissue plasminogen activator was observed in melanoma tissues, cell lines and xenografts, while various inhibitors of fibrinolysis, including α₂-antiplasmin, α₂-macroglobulin, α₁-antitrypsin and antithrombin III, were found intracellularly only in the melanoma tumor cells but not in melanoma cell lines nor in xenografts. We believe that these inhibitors are derived from the blood and are bound to the tissue plasminogen activator within the melanoma cells. Their presence in tumor cells would explain the lack of fibrinolytic activity in melanoma tissues.