The growth and differentiation of the mammary gland is a complex process involving the interactions of various steroid and polypeptide hormones. The mammary growth occurs in a discontinued way during five distinct phases, i.e. fetal, prepubertal, postpubertal, pregnancy, and early lactation periods. The gland expresses its differentiated function by producing milk during the period of lactation. Although the mammary gland has been regarded as one of the well-known target tissues for various types of hormones, evidence has been accumulating in recent years indicating the involvement of other factors and substances in the process of mammary growth and differentiation. In this chapter the importance of the mesenchymal component in mammary epithelial cell growth has been documented. This component, including embryonic mesenchyme and adipocytes in adult tissue, play an essential role by not only serving as a structural entity of the gland but also by producing extracellular matrix substances and various factors that promote the growth, morphologic development and differentiation of mammary epithelium in a paracrine fashion. Other possible paracrine peptide factors for mammary cell growth have been isolated from several other sources including mammary tumors and milk. Thus, it is possible that paracrine growth factors play a role in mammary tumorigenesis. Since most of these factors are present in minute amounts, it is difficult to obtain pure forms of these factors in sufficient amounts for detailed physicochemical characterization. Moreover, further studies are needed to assess the physiological importance of these growth factors, their mode of action, and the mechanism of regulation relating to their production. It is conceivable that some mammary paracrine agents interact with each other or with endocrine agents in promoting the normal and neoplastic growth of mammary cells. Furthermore, the possibility exists that the production and release of paracrine factors are under the endocrine control. In view of the rapid progress and great interest in this area, these questions may be answered before long, along with the discovery of some other new growth regulating agents in this system. Clearly such information is important for understanding the complex process of normal and neoplastic growth of the mammary gland.