Enzymatic activities in a saline-extractable fraction from two polar types of murine lepromas were investigated using pyroglutamyl-glycyl-arginine-p-nitroanilide and plasminogen-rich, as well as plasminogen-free, fibrin plates. An inhibitor activity for urokinase was also measured. C57BL/6NJcl (immunologically high responder strain) mice inoculated with 2 X 10(8) Mycobacterium lepraemurium developed a localized lepromatous lesion after 4 weeks. The tissue extracts obtained after 4-6 weeks exhibited inhibition for urokinase (8.8 IU/mg protein), but no enzymatic activity. After 8-11 weeks, when the lepromas showed an ulcerative change, prominent peptide hydrolytic activity (84.8 nmol/mg/protein/ min) was demonstrated. The fibrin plate assay confirmed that plasminogen activator is predominantly involved (26.4 IU/mg protein). The proteolytic activation was apparently correlated with discharge of purulent materials containing the bacilli and subsequent limitation of leproma development. However, similar modulation of the fibrinolytic enzyme-inhibitor system was not shown in CBA/N mice (immunologically low responders). The tissue extracts showed a low level of urokinase inhibitor activity (1.9 IU/mg protein), but no peptidolytic or plasminogen activator activity. Consequently, lepromas were developed progressively until 25 weeks after infection and dissemination from the lepromatous lesion took place thereafter. In comparison with histologic findings, which revealed accumulation of lymphocytes and mononuclear cells in the peripheral zone of lepromatous lesions in the C57BL/ 6NJcl, but not in the CBA/N mice, a controlling mechanism of plasminogen activator in tissue is assumed to be involved in the development of the granulomatous tissue reaction.