The "nurse cell" concept developed as a result of the morphological relationships between germ cells and Sertoli cells, and because of the junctional barrier defined by Sertoli cells which allowed the creation of a compartment in which the constituents could be regulated by Sertoli cells. The molecular approach to studies of the role of Sertoli cells in spermatogenesis has already led to a better understanding of the "nurse cell" concept. Molecular studies on the function of Sertoli cells have for the most part been dependent on the Sertoli cell culture techniques which were first published in 1975 (Dorrington and Fritz 1972; Steinberger et al. 1975a; Welsh and Wiebe 1975). As a result of this technical innovation Sertoli cells which remained responsive to hormones and which continued to carry on secretory activities could be obtained relatively free of other cell types. In the spent medium from cultured Sertoli cells specific secretion products could be detected such as ABP, transferrin, and SGP-2; components with inhibin-like activity; and metabolic products such as lactate. Thus, for the first time some molecular correlates to the "nurse cell" role of Sertoli cells have been described. In addition to the close morphological relationships between germ cells and Sertoli cells it has now been demonstrated that protein products of the Sertoli cells directly interact with germ cells. The Sertoli cell-mediated iron transport to germ cells via transferrin is the clearest demonstration of this interaction. Both SGP-1 and SGP-2 interact with spermatozoa and can be found tightly associated with the plasma membrane of these cells. As more of the secretion products of Sertoli cells are characterized the important role of these cells in spermatogenesis and spermiogenesis will be underscored. The identification and characterization of the Sertoli cell secretion products is important information to obtain, but an understanding of the function of these products also requires temporal knowledge about their synthesis. The interdependence of the morphological observations of the testis and the new technology of molecular biology is most clearly illustrated by the studies involving quantitative in situ hybridization. This technique has been utilized to quantify the amount of transferrin and SGP-2 mRNA present in Sertoli cells associated with different stages of the cycle of the seminiferous epithelium and to establish positively the Sertoli cell location of a specific mRNA (Morales et al. 1987). The technique is potentially applicable to any Sertoli cell specific protein product for which a cDNA probe becomes available.(ABSTRACT TRUNCATED AT 400 WORDS)