The dissemination of malignant cells throughout the body to form secondary growths is a highly complex process dependent upon both host and tumor cell properties. One potential defensive system which could influence the outcome of metastasis is the mononuclear phagocyte system. Although macrophages have been observed in essentially all primary and metastatic tumors examined regardless of histologic type or anatomic location, the biological significance of these observations is far from clear. What is clear, however, is that in most cases the effects of macrophages on tumor cells are not sufficient to alter progressive growth. Therefore, the presence of macrophages within metastases does not necessarily signify a protective host defensive response. On the other hand, macrophage-induced regression of established metastases can occur in vivo under certain conditions in which tumor-bearing mice are treated systemically with macrophage-activating agents. When mice bearing metastases are treated with macrophage-activating agents contained within liposomes, metastasis-associated macrophages are activated to the tumoricidal state and the metastatic lesions are simultaneously eradicated. Such a process of macrophage activation may have implications in determining successful approaches to the therapy of disseminated cancer.