In all species studied to date, follicular development is the consequence of pulsatile gonadotrophin stimulation occasioned by a GnRH pulse generator located in the mediobasal hypothalamus. This pulse generator operates within a narrow frequency range established by a neuronal system which, in the higher primates including man, discharges with a period of approximately 1 h. This frequency does not appear to change significantly as the follicular phase of the menstrual cycle progresses and plasma oestradiol concentrations rise. When these exceed a defined threshold for approximately 36 h, the pre-ovulating gonadotrophin surge is initiated and ovulation ensues some 24 h later, the so-called positive feedback action of oestrogen. This sequence of events can be replicated experimentally in subjects with various hypothalamic lesions which abolish endogenous GnRH production, simply by the administration of exogenous GnRH at an unchanging physiological frequency. This implies that the site of the positive feedback action of oestradiol is the pituitary gland and that GnRH plays but a permissive role in the initiation of the mid-cycle gonadotrophin surge. This process can be disrupted by a number of inputs which perturb the proper functioning of the hypothalamic GnRH pulse generator.