In an experimental murine metastasis model host pretreatment protocol (HPP) was tested to abrogate lung colonization of tumor cells. The stimulation of the host defense by lentinan or TP4, and the PGI2 administration was effective in the case of the immunosensitive low metastatic tumor. The modulation of the host cells and/or the extracellular matrix by the glycosaminoglycan biosynthesis blocking agent KL-103--but not by the degradation inhibitor suramin--inhibited the lung colonization of the highly metastatic immunoresistant tumor variant. In combination with the cytotoxic antiproliferative agents these non-toxic drugs could be useful in new protocols to prevent tumor dissemination.