We collected multiple samples from 43 human bronchogenic squamous-cell carcinomas and studied the ultrastructure of the tumor-cell-lung parenchyma interaction in the tumor periphery. Since, in the periphery of a growing tumor, the surrounding tissue has only recently been reached by the tumor cells, it is the initial stage of interaction which can be observed here. The main findings were: The tumor cells in the tumor periphery always penetrated the lung parenchyma along the epithelial side of the alveolar basal lamina. The non-neoplastic alveolar epithelial cells were either detached from their basal lamina or overgrown by the tumor cells, without being visibly damaged or destroyed. When the alveolar epithelial cells were overgrown by the tumor, they retracted and formed extra- or intracellular lumina much smaller than the original alveoli. The contact between tumor cells and alveolar epithelial cells resulted in the formation of common desmosomes and complete junctional complexes and the common lining of lumina. Although the tumor cells extended small pseudopods through the basal lamina, they virtually never migrated through it to reach the interstitial compartment. These results indicate that the initial invasion of lung parenchyma is characterized by a smooth integration of tumor cells and elements of the preexisting tissue, leading to orderly associations of neoplastic and non-neoplastic cells, rather than by tissue destruction by the tumor cells.