The relative dependence or independence of the secretion of the neurohypophysial hormones, arginine vasopressin and oxytocin, was investigated using a wide variety of stimuli reported to cause the secretion of one or the other hormone. Differences in species, animal preparations, sampling techniques, assays, and other factors make comparison of many previous studies difficult. The aim of this study was to overcome these problems by using the same methodology, animal species, and assays to compare vasopressin and oxytocin release. To further strengthen the analysis, determinations of vasopressin and oxytocin were done in the same blood samples. The results demonstrated that during simultaneous release of both hormones, vasopressin is released in greater proportion following restraint stress, hemorrhage, isotonic hypovolemia, and nicotine, whereas oxytocin is released in greater proportion following endotoxin or hypertonic saline. Vasopressin was released without oxytocin following diethylstilbestrol. Oxytocin was released without concomitant vasopressin release following exercise, hypothermia, hyperthermia, labour, and lactation. Neither oxytocin nor vasopressin release was observed following thyroid-releasing hormone or insulin-induced hypoglycemia. These data illustrate the marked flexibility of the hypothalamo-neurohypophysial system that regulates secretion of vasopressin and oxytocin.