The scope of the present study was to investigate the interaction between human tumor cells heterotransplanted to athymic mice and the connective tissue supplied by the host animals. Thirteen human tumors of different origin and various histological types were analyzed by light and electron microscopy between days 1 and 30 after transplantation. Constant patterns of histological and ultrastructural changes were observed within all tumors investigated which were characterized by different histological type and varying growth velocity. Following an initial dying of most inoculated tumor cells, host-supplied inflammatory cells immigrated into the xenografts and phagocytozed the necrotic and degenerating tumor cells. Fibroblasts which produced vivaciously collagenous material invaded the xenografts and built up solid strands of connective tissue radiating from the periphery into the xenografts. These cords of connective tissue tightly contacted surviving tumor cells and were used as guide-rails for ingrowing capillaries. Immediately after their immigration into the fibrous strands, first mitoses of tumor cells occurred in close proximity to capillary-conducting strands of connective tissue, resulting in a revival of tumor cell proliferation at first near to the fibrous cords and a spreading of newly formed tumor cells along the strands of connective tissue. These results indicate that the host-supplied connective tissue plays an important role in tumor cell proliferation and local tumor expansion.