We previously established a model to study human tumor spontaneous metastasis in immunosuppressed newborn rats. Different observations suggested that the development of pulmonary metastases of human melanoma cells in this animal might reflect, at least partially, an organ specificity phenomenon. We thus examined the "soil" property of the rat lung in terms of growth stimulating activity and specific interactions between tumor cells and pulmonary cells. We could not demonstrate any melanoma cell growth-promoting activity in lung conditioned medium. On the other hand, tumor cell adhesion was drastically enhanced when measured on pulmonary fibroblast monolayers or derived extracellular matrix. Adsorption of lysates of 7GP122 highly metastatic melanoma variant on viable total lung cells enabled us to detect at least 10 proteins or protein subunits which could specifically interact with pulmonary cell membranes, while only one of these proteins was detectable when the same experiment was performed with control liver cells. Conversely, we could show that there exist several corresponding structures on pulmonary cells which could adsorb on tumor cells. Thus, specific cell surface adhesion molecules, leading to specific adhesion between melanoma cells and pulmonary cells, may lead to preferential metastatic development in rat lung.