A better understanding of the hormonal regulation of spermatogenesis may provide new avenues for management of human infertility, and development of safe and reversible contraceptives. Although much basic work must be conducted in lower mammals, primarily rodents, concepts must, at some stage, be tested for their relevance to humans. In this review, we will draw together existing data in humans and monkeys in formulating an overview of the hormonal regulation of spermatogenesis, focusing particularly on the pursuit of the male hormonal contraceptive. Reference to data from lower mammals will be made when these highlight interesting and relevant differences or similarities with primates. The dual functions of the adult testis; namely, the production of spermatozoa (fertility) and the secretion of testosterone (virility), are both dependent on stimulation by the pituitary gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which are secreted in response to hypothalamic gonadotropin-releasing hormone (GnRH). Testosterone is essential for promoting spermatogenesis and is secreted by the adult Leydig cell under LH stimulation, and acts via androgen receptors (ARs) on Sertoli cells, Leydig cells, and peritubular cells. That testosterone exerts its effects on somatic cells rather than germ cells was highlighted by recent germ cell transplantation studies (Johnston et al, 2001). FSH acts via