Incidence of aseptic loosening of hip prostheses is increasing in recent years. Previous studies suggested the involvement of proteinases and cytokines in the accelerated bone lysis associated with loosening. To investigate the role of matrix metalloproteinases (MMPs) in the loosening, Gelatin/Type IV collagenases, namely, 72 KDa matrix metalloproteinase (MMP)-2 type and 92 KDa MMP-9 type were analyzed in 14 cases of the loosened endoprostheses of the hip. Zymographic and densitometric analyses revealed production of MMP-2 ancl elevated induction of MMP-9 in tissue extracts from both the interface hetween hone and implants and the capsular tissues when compared with those in synovium obtained from a patient with a t'ractured femoral neck. MMP-9 showed stronger activity than MMP-2. In the sample of a fractured femoral neck, MMP-2 was detected, but MMP-9 was not detected. In matched samples, the activity of MMP-2 and MMP-9 in the interface tissues showed stronger activity than those in the capsular tissues. There was no difference between cemented and uncemented femoral prostheses. The state of prostheses(loosening, osteolysis, and cup wear) did not influence on the activity of MMP-2 and MMP-9. Theses findings suggest a role for MMP-2 and MMP-9 type gelatinase/Type IV collagenases in the degradation of extracellular matrix of periprosthetic tissues, where they may cause weakening of the connective tissue hed and the loosening of total hip replacement endoprostheses. Consequently. we could confirm the role of MMP cascade in aseptic loosening of total hip prostheses. The further study ahout other types of MMP and the inhihitor of MMP will be needed.