Giant cell arteritis (GCA) is a relatively common granulomatous arteritis of unknown etiology which mainly occurs in elderly people. Using histopathological findings from-seven biopsy cases of temporal artery and one autopsy case of GCA, and performing immunocytochemical staining for matrix metalloproteinase (MMP)-2 and -9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 and -2, we tested the hypothesis that an imbalance between MMPs and TIMPs may be a critical determinant in developing severe intimal hyperplasia and luminal stenosis. All biopsy cases revealed nearly complete luminal occlusion of the temporal artery with active lymphocytic infiltrate, fragmentation of internal lamina and median elastic fibers. Four of seven cases revealed typical GCA. The autopsy case was systematically sampled for histological examination, revealing GCA in the ascending aorta, main branches of aorta and coronary artery. Immunocytochemical staining revealed intense staining for MMP-2 and -9 in fragmented media of the aorta and artery, and less positive staining for TIMP-1 and -2 at the MMP-positive media. In situ hybridization revealed intense positive staining for TIMPs in GCA despite weak immunocytochemical staining for TIMPs. Control cases were negative for TIMPs by immunocytochemical staining whereas RNA message level was mildly positive at a lesser intensity than that of GCA. Granulomatous tissue of fibroblasts and giant cells were most intensely positive for MMPs. The presence of markedly increased MMPs and less increased TIMPs in GCA may implicate an MMPs-TIMPs imbalance in the pathogenesis of GCA.