Matrilysin is a member of the matrix metalloproteinase gene family, which is believed to play an important role in tumor invasion and metastasis. We examined the effects of over- and under-expression of matrilysin on the ability of colon cancer cells to migrate across an artificial membrane in vitro. Introduction of matrilysin caused colon cancer cells to become more invasive as assessed by an in vitro invasion assay. In contrast, expression of matrilysin was down-regulated by all trans-retinoic acid or by introduction of anti-sense matrilysin in BM314 colon cancer cells. This down-regulation caused these cells to become less invasive. We demonstrated a correlation between matrilysin level and the invasive potential of human colon cancer cells, implying an important role for matrilysin in the control of tumor invasion in vitro.