The classical concept that the control of follicle-stimulating hormone (FSH) and luteinising hormone (LH) secretion by the pituitary gland is achieved by the stimulation of gonadotropin-releasing hormone (GnRH) and negative feedback by steroid secretion from the gonads has recently been modified by the identification of several proteins with the capacity to modulate FSH secretion. These proteins, inhibin, activin and follistatin, are produced in the ovary and testis and have the capacity to act as long loop protein feedback signals which modulate FSH secretion. Further studies indicate that inhibin probably acts as a circulating hormone to inhibit FSH secretion. More recent data suggest that activin and follistatin may act as local mediators to control FSH secretion at the pituitary by paracrine or autocrine phenomena. The production of activin, which stimulates FSH, and its binding protein follistatin, by pituitary cells raises the possibility that the local production modulates FSH secretion in addition to the long loop feedback signals emanating from the gonads through the steroid hormones estradiol and testosterone as well as circulating inhibin levels. Further studies are necessary to confirm the nature of these regulatory processes.