The classical image of the endocrine system is that secretory function of a gland is regulated from outside that gland by other organs. Focused on the pituitary gland, hormone secretion by the anterior lobe is under control of peptides and biogenic amines produced by the hypothalamus. About a decade ago, our group launched the new idea that functioning of the anterior pituitary (AP) is also regulated from within, i.e., that the constituent cell types inter-communicate to control hormone secretion. Extensive in vitro research has now provided a body of evidence that paracrine communication plays an important role, not only in regulation of hormone secretion but also in development, growth, and differentiation of the AP [reviewed in Denef(1994) The Pituitary Gland, pp. 351-378]. It further revealed that crosstalk between the cells is mediated by local, paracrine, factors. The main objective of our research is to identify those factors, their actions and the producing and target cell type(s) in order to unravel the paracrine communication network that is functional in the AP. Equally important, we set the step towards in vivo examination of the results obtained in vitro using transgenic mice. In the present article, we will review the technology used, three examples of AP cell-to-cell interactions studied, and we will discuss the value of transgenic animal models in the study of AP paracrine communication. (C) 1997 Wiley-Liss, Inc.