As soon as scientists began to study testicular structure and function, the concept emerged that SCs and GCs communicate. We now know that the seminiferous epithelium is certainly one of the most complex tissues and that the structural and functional supports of SC-GC communication are extremely elaborate. At all stages of sexual maturation, somatic cells and GCs have developed a formidable set of communication devices that are involved in attachment, displacement, cell shaping, and cell-cell transfer of molecules and cellular materials. Some of the best morphologists since the nineteenth century have studied the anatomical basis of the SC-GC dialogue and have laid the foundations to the understanding of the spermatogenic process. Further experimental efforts are still being made. In particular, new data are emerging that have enabled scientists to go beyond the descriptional or deductive aspects and to tackle the mechanical aspects. From the functional point of view, significant progress has been made in deciphering SC-GC cell language. The unique strategic position of the SC allows this cell type to receive, integrate, and emit all the signals required for the spermatogenic process to or from the extratubular compartment (e.g., FSH, testosterone), the peritubular cells (e.g., P-Mod-S), and GCs themselves. Its location also allows it to coordinate GC activity in both the transversal and the longitudinal axes of the seminiferous tubule. The SC barrier and SC products create the physical and chemical microenvironments required for the completion of each of the different steps of spermatogenesis. In addition to the tubule fluid, the SC products directly or indirectly implicated in GC control are proteins, peptides, and steroid(s) involved in germ cell proliferation, differentiation, and metabolism; transport/binding proteins; proteases; extracellular matrix components; energy metabolites; antiproteases; and various membrane components. Sertoli cell polarization results from the existence of SC-SC occluding junctions. The products required for the mitotic phase of spermatogenesis may principally be secreted basally, whereas those required for meiotic division, spermiogenesis, and sperm cells may preferentially be secreted apically. The interaction between SC factors and GCs is mediated by GC membrane receptors and different endocytic processes. The GC secondary pathway(s) involved in SC action remains a mystery. Germ cell markers that would enable a precise assessment of SC influence are lacking. Changes in the composition of the GC complement and in GC size and shape, as well as GC divisions and migration, profoundly affect SC morphology and function.(ABSTRACT TRUNCATED AT 400 WORDS)