The central role of the mammalian hypothalamic-pituitary axis in regulating female reproductive cycles is reviewed. A variety of animal models and techniques that offer increased sensitivity, speed, and flexibility over traditional reproductive toxicologic approaches for short-term testing or screening are discussed, including the pivotal analysis of gonadotrophin releasing hormone (GnRH) pulse generator activity in vivo and in vitro. Other neuroendocrine techniques that require further development, but provide potential approaches to demonstrate specific sites or mechanisms of action for toxic effects on the hypothalamic-pituitary axis are suggested.