The relation of neuroendocrine functions to the reproductive decline was compared in human subjects and in rats of both sexes. The ovaries of rats remain potentially functional throughout the animal's life span, but cease to exhibit regular 4- or 5-day cyclic changes at about midelife. The loss of estrous cycles is believed to be due primarily to changes in hypothalamic neurotransmitters that lead to failure to exhibit cyclic surges in release of hypothalamic luteinizing hormone-releasing hormone and pituitary gonadotropins. Menstrual cycles normally cease in women between 40 and 50 years of age, primarily because the ovaries decline in their capacity to respond to gonadotropic stimulation with adequate production of estrogen and progesterone, and by ovulation, which in turn leads to increased gonadotropin secretion. In aging male rats, testosterone secretion by the testes decreases due to reduced stimulation by gonadotropins, in turn caused by decreased hypothalamic stimulation. Elderly men have been reported to show a reduction in testosterone and sperm production, accompanied by an increase in gonadotropin secretion, but more recent work in healthy, active men showed no increase in testosterone secretion with age.