Publisher Summary This chapter focuses on the immunophysioloy of the male reproductive tract.. The male reproductive tract poses a challenge to the immune system not presented by most other organ systems and tissues. The human testis produces approximately 100 million highly differentiated sperm each day from a pool of no more than a few hundred thousand spermatogonial stem cells, a level of productivity matched in output and complexity only by the hematopoietic system. In contrast to the hematopoietic tissues, or any other organ in the body, these differentiated cells first appear very late in developmental life, at the time of sexual maturation, long after the maturation of the immune system and the establishment of systemic immune tolerance. In humans, the period between the perinatal editing of the lymphocyte repertoire and the first appearance of significant numbers of the earliest meiotic germ cells (the spermatocytes) is usually more than 10 years. As a consequence, these cells and their progeny express a broad range of novel structural proteins, surface receptors, signaling molecules, and enzymes that have the potential to be seen as foreign by the mature immune system.