In considering the factors which influence the response of animals to oestrogens Marrian & Parkes [1929] were of the opinion that previous dosage was unimportant. Emmens [1939] has recently reconsidered this question and has arrived at similar conclusions. In contrast with these experimental findings we have observed clinically that prolonged courses of administration of oestrogens in high doses are followed by a diminution in response. The following experiments were devised to examine the behaviour of ovariectomized mice after similar treatment. Material and Methods The animals used in the experiments were adult female mice obtained from dealers. Vaginal smears were taken daily by washing the vagina with a small quantity of normal saline contained in a sterile pipette, and were read unstained. Those animals showing regular cycles were ovariectomized. Oestrogenic treatment was begun within 3 days of the operation. Oestrone (Menformon kindly supplied by Organon Ltd.) was used in aqueous solution