The "nurse cell" function of Sertoli cells in spermatogenesis was originally tacitly assumed on the basis of the anatomical relationships between cells in the testis. In mammals, from very early in prenatal development to the onset of meiosis and to the ultimate production of spermatozoa, the relationship between the germinal cells and the Sertoli cells is important and apparently obligatory. The experimental evidence supports the notion that the primary endocrine regulation of spermatogenesis via FSH and testosterone is manifested through actions on the Sertoli cells. Although diverse strategies are used by Sertoli cells to support germ cell development, one of the most important roles of Sertoli cells is the regulation of the intratubular and intercellular environment adluminal to the tight junctional complexes. The meiotic and post-meiotic germ cells are sequestered by Sertoli-Sertoli junctional complexes in an adluminal compartment that is isolated from the serum or lymph. As a result of this sequestering activity, the secretion products of the Sertoli cells and the meiotic germ cells determine the composition of this local environment that can influence meiosis as well as spermatid and spermatocyte development. Evidence is accumulating that paracrine and autocrine factors from Sertoli and germ cells are important in the functioning of both cell types. While it is important to know what Sertoli cells and germ cells make, it is equally important to know when they make it. Distinct but well-defined groups of germ cells interact with Sertoli cells in a cyclic pattern. These recurring groups of germ cells define the cycle of the seminiferous epithelium during which sperm are produced in an asynchronous fashion.(ABSTRACT TRUNCATED AT 250 WORDS)