Background Previous studies on atherectomy specimens from patients with acute coronary syndrome (ACS) implicated the role of proteolytic enzymes. We examined whether the plasma levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were increased in the coronary circulation in ACS. Methods and Results The plasma levels (nanograms per milliliter) of MMP-9 and TIMP-1 in the aorta (Ao) and great cardiac vein (GCV) were measured in 29 patients with ACS (20 with acute myocardial infarction [group 1] and 9 with unstable angina [group 2]), 17 with stable effort angina (group 3), and 20 control subjects (group 4). Group 1 patients had occlusion in the left anterior descending artery (LAD), and groups 2 and 3 patients had culprit lesion in the LAD. In group 1 blood samples were obtained at the time of direct coronary angioplasty done within 12 hours after the onset. The Ao level of either MMP-9 or TIMP-1 did not differ among the 4 groups. The GCV-Ao differences in MMP-9 and TIMP-1 were both significantly increased in groups 1 and 2 compared with those in group 4. Neither of them was different between groups 3 and 4. Neither the GCV-Ao difference in MMP-9 or TIMP-1 level was correlated with the maximal creatine kinase level in group 1. Conclusions Increased plasma levels of MMP-9 and TIMP-1 were detected in the coronary circulation in ACS patients, suggesting a process of active plaque rupture in ACS. (Am Heart J 2001;141:211-7.)