Gonadotropin secretion during the post-menopausal period is considerably higher than during the reproductive years. In this study, we present evidence that changes in the hypothalamic-pituitary-ovarian unit occur over a period of years before the onset of menstrual irregularity which heralds the menopause. FSH and LH were measured in blood samples taken on 6 days during the mid-follicular phase from 127 regularly cycling women aged between 23 and 49 yr. The women aged 23-30 yr were taken as the control group and the remainder were grouped in 2-yr age bands. A significant increase in FSH underwent a further increase in the oldest group (48-49 yr) in whom LH also became significantly elevated. The difference in the timing of the change in FSH and LH concentrations was related not only to chronological age but also to the number of years before the menopause. The increase in FSH occurred 5-6 yr pre-menopause, that in LH not until 3-4 yr before the cessation of menstruation. It is concluded that an early sign of the aging of the reproductive mechanism can be detected in women who are having normal ovulatory cycles. The regulation of FSH and LH secretion appears to be sufficiently independent to permit the observed differences in the age of onset of these premenopausal increases.