Mouse mammary tumors grow preferentially upon transplantation into intact mammary glands compared to cleared mammary fat-pads. Both sites provide stroma of the orthotopic site, but the latter lacks epithelial elements. If epithelium from enzymatically dissociated normal mammary glands is added to the tumor cells prior to injection into cleared fat-pads, tumor growth is comparable to that seen in intact mammary fat-pads. The growth-enhancing effects of normal mammary cells are not duplicated by normal kidney or liver cells. These results demonstrate that epithelial-epithelial interactions, as well as stromal-epithelial interactions, are associated with the enhanced growth of mammary tumor cells transplanted into orthotopic sites. The results also suggest that enhancement of tumor growth does not require intact tissue architecture.