Estrogen treatment of ovariectomized female rats for a week decreased plasmaosmolality from 294 to 278 mosmol/kgH2O, but recordings from the whole animalpreparation under urethan anesthesia failed to detect any change in theactivity of 76 vasopressinergic neurons in the supraoptic nucleus (SON) ofthe hypothalamus. In brain slice preparations, neuronal discharge of 74presumed vasopressinergic SON cells increased linearly as the osmolality ofthe perfusate was increased from 278 to 320 mosmol/kgH2O, each 10mosmol/kgH2O fraction corresponding to a 0.7-Hz change. Thisosmolality-neuronal activity relationship was similar in the slices takenfrom the estrogen-treated and the control ovariectomized animals, except thatthe neurons in the former fired twice as frequently as those in the controlthroughout the osmolality range. This difference explains theestrogen-induced decrease in the osmolality threshold to elicit antidiuresisand the resultant water retention in estrogen-treated animals. It wasreasoned that the estrogen-induced neuronal activation was offset by thedecreased plasma osmolality in the animal as a whole.