Stress is revealed by the inability of an animal to cope with its environment, a phenomenon that is often reflected in a failure to achieve genetic potential. Field data from dairy cows show that stressors such as milk fever or lameness increase the calving to conception interval by 13-14 days, and an extra 0.5 inseminations are required per conception. We suggest that a variety of endocrine regulatory points exist whereby stress limits the efficiency of reproduction. Transport produces an immediate constant increase in arginine vasopressin (AVP) and corticotrophin-releasing hormone (CRH) secretion in ewes, but adrenocorticotrophic hormone (ACTH) reaches a maximum in the first hour while cortisol is highest during the second hour. In contrast, after an insulin injection, the hypothalamo-pituitary-adrenal (HPA) response is delayed occurring only after glucose decreases below a threshold. Changes in AVP, CRH and ACTH each follow a similar time course, but eventually the secretion of AVP and CRH decreases while glucose is still at a nadir. Negative feedback effects appear to operate mainly at the pituitary level during transport but at the hypothalamus during hypoglycaemia. We also have endocrine evidence to show that stressors interfere with precise timings of reproductive hormone release within the follicular phase. Transport, or insulin, reduce the frequency and amplitude of gonadotrophin-releasing hormone and LH pulses, suggesting that these stressors exert effects at the hypothalamus or higher centres in the brain. Both stressors also delay the onset of the luteinising hormone (LH) surge. Preliminary results suggest that opioids mediate these effects but progesterone/glucocorticoid receptors are not involved because the antagonist, RU486, is unable to reverse insulin-induced delays in the LH surge. There is also evidence to support effects at pituitary level because exogenous ACTH, or transport, reduce the amount of LH released by challenges with GnRH. The reduction in endogenous GnRH/LH secretion ultimately deprives the ovarian follicle of adequate gonadotrophin support leading to reduced oestradiol production by slower growing follicles. Thus, there is a level of interference by stressors at the ovary. Reproduction is such an important physiological system that animals have to ensure that they can respond to their surroundings; thus, it is advantageous to have several protein mechanisms, i.e. at higher brain, hypothalamus, pituitary and target gland levels. However, when pushed too far, subfertility occurs.