On completion of spermatogenesis, testicular spermatozoa appear structurally mature but are infertile and must undergo a sequential maturational process in the epididymis to become motile and acquire fertilizing potential. This chapter provides a cell biological overview of the endocytic and secretory activities, along the extratesticular duct system, that provide appropriate conditions for epididymal maturation of bull spermatozoa. The compartmentalization of the bovine epididymis is illustrated and discussed in terms of epithelial cell types and merocrine and apocrine protein secretions by principal cells that influence maturation. Sequential maturational events are followed with examples, first, of testicular proteins associated with spermatozoa that are endocytosed to form a ‘clean slate’ and then, of epididymal secretory proteins that recondition the sperm milieu and bind to spermatozoa in order to attain its full fertilization potential. Finally, an assessment is made of the potential contributions to epididymal maturation of some well-characterized and identified secretory proteins that interact with the cytoplasmic membrane of spermatozoa.