The human testis has been evaluated by its endocrine function, daily sperm output in ejaculates, general appearance of seminiferous tubules, differential cell counts in the testis, and daily sperm production. Within-subject variation for total sperm count in ejaculates is extremely high at 42% to 75% coefficient variation. This variation can be reduced to 12% by averaging the counts obtained for the last three of five daily ejaculates. Plasma FSH concentrations are particularly useful in assessing the status of seminiferous epithelium and/or its Sertoli cell function in infertile men. In aged men, plasma LH, FSH, and estradiol concentrations are higher while plasma testosterone, free testosterone, and the ability of the testis to secrete testosterone following stimulation are reduced. Other age-related changes in human testes include a high incidence of azoospermia, reduced sexual activity, reduced testicular size, impaired spermatogenesis, reduced tubular length, increased thickness of tubular boundary tissue, sclerosis, focal mononuclear orchitis, and dilation of the rete testis. Due to the long duration of the spermatogenic cycle and low numbers of germ cells in human testis, daily sperm production per g parenchyma (efficiency of spermatogenesis) is much lower in humans than in other species. Testicular parenchymal weight, proportion of testis occupied by seminiferous epithelium, volume of seminiferous epithelium, and daily sperm production are significantly reduced in aged men. In various species, including man, germ cell degeneration occurs during spermatocytogenesis, meiosis, and/or spermiogenesis. Germ cell degeneration plays a pivotal role in spermatogenesis, but the mechanisms of degeneration, its etiology, and approaches for its prevention remain unclear.