The role of stromelysin-3 (MMP-11) in plasminogen/plasmin and matrix metalloproteinase system function was investigated with the use of MMP-11-deficient (MMP-11(-/-)) mice. Haemostasis analysis of blood and plasma obtained from wild-type (MMP-11(+/+)) or MMP-11(-/-) mice did not reveal significant differences. Urinary u-PA antigen (380-600 ng/ml) and activity levels (62-65 IU/ml) were comparable. Vascular tissue-type (t-PA) or urokinase-type (u-PA) plasminogen activator activities were not significantly different in aorta extracts of MMP-11(+/+) or MMP-11(-/-) mice. In vivo thioglycollate-stimulated macrophages of both genotypes expressed comparable u-PA-mediated plasminogen activating potential and fibrin or extracellular matrix degrading capacity. Organ sections did not show significant fibrin deposition in the liver of MMP-11(+/+) or MMP-11(-/-) mice. In purified systems, a murine MMP-11 fragment containing the catalytic domain degraded fibrinogen, mainly by cleavage of the A alpha-chain, but did not significantly lyse fibrin. Active and latent MMP-2 (gelatinase A) and MMP-9 (gelatinase B) levels were comparable in aorta extracts of MMP-11(+/+) and MMP-11(-/-) mice. Cell culture experiments confirmed comparable ratios of active versus latent MMP-2 and MMP-9 in fibroblasts, smooth muscle cells and macrophages derived from both genotypes. These data suggest that fibrinolytic activity mediated via the plasminogen/plasmin system does not require MMP-11, and that MMP-11 does not play a major physiological role in the expression or activation of gelatinases.