Conflict of interest: No conflict of interest has been declared. Nonstandard abbreviations used: filipin-sterol complex (FSC); protein kinase A (PKA). epididymal sperm undergo dramatic alterations in their membrane sterol content. Such changes are highly species-specific and are also highly specific with regard to the class of sterol that is being changed (10). In addition, intracellular signaling systems that control capacitation mature during epididymal transit (ref. 11; M. Fornes et al. unpublished data). How alterations in membrane sterol composition integrate with the maturation of signaling pathways is still not fully understood. The majority of alterations of epididymal sperm sterol content probably result from interactions of the sperm with the epididymal epithelium. Epithelial linings of both the epididymis and the vas deferens appear to have a highly developed sterol-producing capacity (12), although the impact of sterol synthetic capacity in the vas deferens on sterol levels in ejaculated sperm is unclear. There are also changes in the content of other sperm lipids during epididymal maturation. In some species, phospholipids are the major source of energy for endogenous oxidative respiration and therefore phospholipid levels decline during epididymal maturation (13). Changes in either sperm sterol or phospholipid levels might serve to alter the membrane cholesterol/phospholipid molar ratio, which has been implicated in the regulation of capacitation, as described below. Given the species-specific nature of these large-scale alterations in lipid content, it is difficult to speak generally about their function. However, in all species examined thus far, cauda epididymal sperm possess clearly delineated membrane domains that differ in their sterol composition. Initially characterized by the presence of filipin-sterol complexes (FSCs) visible by freeze-fracture electron microscopy, these domains impart heterogeneity on the sperm surface within a given region of these cells. Such subdomains suggest the possibility of still more precise compartmentalization of function beyond the obvious polarization of these cells into head and tail domains that contribute to egg interaction and motility regulation, respectively. Indeed, these subdomains have recently been hypothesized to act as scaffolds or foci for signaling pathways regulating sperm capacitation in both the head and flagellum (14).