The purpose of this study was to determine whether the in vitro interaction of tumor cells with an organ fragment correlated with organ colonization in vivo. Several clones of the K-1735 melanoma that exhibit different potentials for lung colonization or the heterogeneous M-5076 reticulum cell sarcoma which preferentially colonizes the liver, were used. The simultaneous subcutaneous implantation of a lung fragment with high lung-colonizing K-1735 cells stimulated the production of tumors, but this was not the case with the M-5076 cells, which do not colonize the lungs after intravenous injection. The ability of the tumor cells to survive in vitro in a lung fragment correlated with their capacity to produce lung tumor colonies after intravenous injection. Moreover, lung-conditioned medium stimulated the growth of lung-colonizing K-1735-M2 cells but not liver-colonizing M-5076 cells. Collectively, the data suggest that tissue-mediated growth stimulation may be one of the factors influencing the metastatic pattern and potential of tumor cells.