Tumor cells and fibroblasts were isolated from the tumor-host interface of a colon 4047 tumor growing subcutaneously in a Fischer 344 rat. The populations were co-cultured to recapitulate the tumor-host interface in vitro. The co-cultured populations grew in a predictable pattern with tumor cells forming nodules surrounded by fibroblasts. Population dynamic experiments demonstrated the fibroblasts enhanced the growth of the tumor cells but tumor inhibited and ultimately destroyed the fibroblasts. Video microscopic examination of the fibroblasts demonstrated intense membrane ruffling adjacent to the tumor nodules followed by membrane fragmentation and detachment. Immunohistochemical staining for gelatinase A was markedly positive within the fibroblasts surrounding the tumor nodules; but negative within the tumor and in fibroblasts when tumor was absent. This technique recapitulates many aspects of the tumor-host interface in vitro and may be a useful model for evaluating several aspects of tumor-host interaction.