To clarify the physiological role played by neutrophil lysosomal protease in cultured human umbilical vein endothelial cells (HUVEC), we studied the effects of cathepsins B and D released from activated polymorphonuclear leukocytes on the fibrinolytic system in HUVEC. Cathepsins B and D reduced the antigens of tissue-type plasminogen activator, and they increased both the antigens and the activity of plasminogen activator inhibitor-1. These results suggest that cathepsins B and D are involved in the thrombotic tendency, since they inhibited the fibrinolytic system in cultured HUVEC.