Hormonal dependency of normal mammary epithelium is a retained characteristic of some but not most mammary tumors. The mechanism by which loss of hormone dependency occurs is unknown but is of great clinical significance for the breast cancer patient. In attempts to elucidate this mechanism, comparisons are being made of the 1) cellular composition, 2) the extracellular matrix production, 3) the growth factor production and requirements and 4) the characteristics of the receptor systems of hormone dependent (primary NMU-induced) rat mammary tumors. The primary tumors consist of both epithelial and myoepithelial-like cells, are estrogen receptor positive, synthesize and require type IV collagen for growth and produce a sarcoma growth factor-like substance. The hormone independent, transplantable NMU tumor possesses no myoepithelial component, neither synthesizes nor requires type IV collagen for growth, is estrogen receptor negative and produces little or no sarcoma growth factor-like substance. We tentatively propose that hormone dependency may be related to the presence of the myoepithelial-like cells in tumors. These cells synthesize type IV collagen and the sarcoma growth factor-like component in culture.