Interaction of stroma and tumor cells within a carcinoma can influence tumor growth and progression. We investigated possible influences of allogeneic and autologous fibroblasts on established squamous cell head and neck carcinoma lines (SCHNCL) and freshly isolated cells from such tumors. Tumor cells were compared in their colony-forming ability, starting from low cell counts, in their ability to form multicellular spheroids (MCS) and in their capacity to form tumors in the subrenal capsule of nu/nu mice. All tumor cell lines tested had a weak plating efficiency, whereas the capacity to form MCS as well as growth and progression in the xenotransplantation model showed large differences. The fibroblasts produced soluble factor(s) which increased colony formation of all tumor cell lines tested to the same extent, whereas admixture of fibroblasts exhibited a different influence on the MCS size and growth. They accelerated growth of the slowly growing MCS but did hardly alter growth of the fast growing ones. Tumor cells growing invasively in the xenotransplantation model were not influenced by coinoculation with fibroblasts; other tumor cells did not produce detectable tumors in nude mice or formed nodules well separated from the renal tissue: adding fibroblasts to these cells caused invasive growth of xenografts. The growth-promoting effects of fibroblasts in these extracorporeal systems might be of prognostic or even therapeutic benefit if intervention of these properties were successful.