Membrane-type matrix metalloproteinase (MT-MMP) is a novel membrane bound member of the MMP family that was identified in tumor cells in 1994. MT-MMP activates pro-MMP-2 thus facilitating tumor cell invasion and metastasis. Various MMP's are expressed in human atherosclerotic plaques where they may play a role in matrix remodeling and plaque disruption, but expression of MT-MMP in human atherosclerotic plaques has not been reported. Therefore, we examined human coronary atherosclerotic plaques and normal arteries for expression of MT-MMP as well as MMP-2 using specific monoclonal antibodies and immunohistochemistry. Both negative and positive controls (tumors) were used. Localization of MMP's was identified using macrophages (MO) and smooth muscle cells (SMC's) specific antibodies. Normal arteries showed the normal distribution of MMP's exclusively within the adventitia. Expression of MT-MMP as well as MMP-2 was found in both MO and SMC's in atherosclerotic plaques within cell-rich regions. The expression of MT-MMP and MMP-2 by MO and SMC's was also demonstrated in cell-culture studies using immunocytochemistry and Western blotting.Conclusion: We show that MT-MMP is expressed by macrophages and SMC's in atherosclerotic plaques and in cell-culture. MT-MMP may have a role in the regulation of matrix turnover in atherosclerosis by providing a mechanism for activation of pro-MMP-2.