Purpose: Degradation of extracellular matrix is considered to be essential process for tumor invasion and metastasis. Activities of matrix metalloproteinases (MMPs) which has a capability of degradation of all matrix components are regulated by activators and inhibitors such as tissue inhibitors of metalloproteinases (TIMPs). Our previous study showed that pro MMP-9 was activated by MMP-3 directly. To clarify clinical significance of MMP-9 and MMP-3 expression in colorectal cancer, we have studied MMP-9 and MMP-3 expression immunohistochemically.Methods: Paraffin embedded spicemens from 194 patients with colorectal cancer who were underwent operation between 1988 and 1991 were immunostained for MMP-9 and MMP-3.Results: MMP-3 was localized only in stromal cells such as monocyte, macrophages, whereas MMP-9 was noted in both tumor cells and stroma. The incidence of MMP-9 expression in the tumor cells was 39.7% and that of MMP-3 in the stroma was 22.2%. There were strong relationship between liver metastersis and the expression of MMP-9 and/or MMP-3. In interest colon, both enzymes significantly coexpressed.Conclusion: MMP-9 and MMP-3 may play an important role in liver metastasis and tumor invasion. In particular, MMP-3 may act as an activator for proMMP-9.