The duration of pseudopregnancy in the rat was extended significantly following unilateral as well as bilateral hysterectomy. These findings suggest a relationship between the quantity of functional uterine tissue and the duration of pseudopregnancy. The initiation of luteal regression during pseudopregnancy occurred earlier as the amount of nontraumatized endometrium increased. Prolactin was capable of overriding the initiation of the luteolytic action of the nontraumatized horn in animals with decidual tissue present in the other horn. In animals with uterine autotransplants an inverse relationship was observed between the quantity of endometrial glands and the duration of pseudopregnancy. These results suggest the production of an active luteolytic substance by the endometrium. When endometrium is converted to decidual tissue it seems to lose this action. (Endocrinology 74: 501,1964) A FUNCTIONAL relationship has been established between the uterus and the corpora lutea in several species (1-4). Following hysterectomy in some animals, the life span of corpora lutea is prolonged. The nature of the physiologic control by which the uterus influences luteal maintenance or regression remains to be determined. Persistence of corpora lutea following hysterectomy may be due to a uterine sparing effect on hypophysial secretion (5) or the absence of a luteolytic substance which induces luteal regression (6). It has been reported by Bradbury (7) that pseudopregnancy is extended in the hysterectomized rat. According to Velardo et al. (8), the duration of pseudopregnancy in this species is not altered following removal of nontraumatized uteri from pseudopregnant rats or complete hysterectomy on the ninth day of pseudopregnancy in animals with unilaterally or bilaterally traumatized uteri. This study was undertaken to determine the effect of hysterectomy at different times during pseudopregnancy on the life span of rat corpora lutea and the relation of endometrium and decidual tissue to luteal regression. Received October 15, 1963. 1 Journal Paper No. J-4603 of the Iowa Agricultural and Home Economics Experiment Station, Ames, Iowa. Project No. 1325. Supported by USPHS, National Institutes of Health (Grant AM-03730), Ciba Pharmaceutical Products, Inc., Summit, N. J., and American Cyanamid Co., Princeton, N. J. Materials and Methods Mature (200-275 g) female rats (Holtzman strain) were maintained on Purina laboratory rat chow ad lib. Illumination was controlled to provide 14 hr of light per day. Pseudopregnancy was induced by mating with vasectomized males. Day 1 of pseudopregnancy was designated as the day following the first fully cornified smear of the estrous period during which mating occurred, and the terminal day was the day of the next proestrous smear (nucleated epithelial cells). Unilateral (subtotal) and bilateral (complete) hysterectomies were performed on day 5 of pseudopregnancy. Bilateral hysterectomies were also made on days 9, 11 and 13 to determine if the time of uterine removal altered the response. Uterine horns were severed at the tubo-uterine junctions and just anterior to the cervices. Ether anesthesia was used. Decidual response was induced by transverse insertion of silk threads in one or both uterine horns on day 5 of pseudopregnancy to determine its effect on the duration of pseudopregnancy (8). Yochim and De Feo (9) suggest, however, day 4 of pseudopregnancy as the optimum stage for induction of the decidual response. The nontraumatized horn was removed in one group and a decidual response was induced in the other horn. Two thirds of a nontraumatized horn was removed prior to mating in another group and traumatization was induced on day 5 of pseudopregnancy. Prolactin and/or lysine vasopressin, dissolved in saline, was injected subcutaneously once daily into rats with one traumatized uterine horn. Hormone treatment began on day 10 of pseudopregnancy and continued to recurrence of estrus. Auto transplantation of the uterus in the rat