Tissue-type plasminogen activator (t-PA) is involved in the lysis of blood clots (fibrinolysis) and is used clinically for this purpose. Endothelial cells are one source of the t-PA present in blood. We report here that interleukin-4 (IL-4) (0.1 to 0.25 U/mL; 1 to 3 x 10(- 11) mol/L), but not interferon-gamma (IFN-gamma), elevates t-PA messenger (m)RNA expression and secretion of t-PA activity by human monocytes, with the maximum response at 2.5 U/mL. Supernatant t-PA activity was detected within three hours of exposure to IL-4 and maximum activity within six hours. Thus, IL-4 may control fibrin deposition at sites of inflammation during cell-mediated immune responses, as well as having a therapeutic role in thrombolysis.