Matrix metalloproteinases 2 and 9 (MMP 2 and -9) have been implicated in the pathogenesis of atherosclerosis and aneurysm formation. The goal of the study was to establish the role of these metalloproteinases in both human atherosclerotic and non-atherosclerotic cerebral aneurysms. Eleven cerebral aneurysms (four atherosclerotic, seven non-atherosclerotic) were immunohistochemically stained for MMP 2 and -9. As controls, atherosclerotic and normal Circle of Willis arteries were similarly immunostained. All specimens were retrieved at autopsy and were paraffin-embedded. In order to evaluate the real MMP 2 and -9 activities, gelatin zymography was also performed in only two available specimens of non-atherosclerotic intracranial aneurysms, because of the relative unavailability of fresh intracranial aneurysm tissue (i.e. reluctance to excise the aneurysm fundus at surgery). Our data establish that MMP 2 and -9 were expressed minimally or not at all in normal Circle of Willis arteries but were strongly expressed in medial smooth muscle cells of atherosclerotic Circle of Willis arteries. In the aneurysm group, both MMP 2 and -9 were strongly expressed in the atherosclerotic aneurysms, but MMP 2 alone was detected in the non-atherosclerotic aneurysms. Zymography revealed a weak enzyme activity correlating to MMP 9 standard recombinant protein. MMP 2 activity was not demonstrated in either specimen. This study shows that the expression of MMP 2 and -9 is associated with atherosclerosis, be it in aneurysmal or non-aneurysmal cerebral vessels but MMP 2 appears to be specifically expressed in aneurysms devoid of atherosclerosis perhaps suggesting a pathogenic role for MMP 2 in the alteration of the extracellular matrix of cerebral arteries during aneurysm formation.