An inverse relationship was observed in guinea pigs between the life span of the corpora lutea and the quantity of uterine tissue remaining following removal of various portions of the uterus at day 5 or 6 of the estrous cycle. There was no apparent relationship between the location of the remaining uterine segment and the persistence of the corpora lutea. Six of 8 completely hysterectomized animals exhibited estrus 63–98 days (average 83 days) following the preoperative estrus, whereas the other 2 animals had not shown estrus when sacrificed at 130 days. Histologic study showed that the corpora lutea and follicles of completely hysterectomized animals were similar to those observed in animals near the middle of gestation. Chemical destruction of the endometrium produced effects similar to those of hysterectomy. These data suggest a functional relationship between the endometrium and the life span of the corpora lutea. Unilateral ovariectomy at the time of partial hysterectomy shortened the life span of the corpora lutea to 18 days as compared with 22 days following partial hysterectomy alone (P < 0.05). Estrous cycle length was not affected by unilateral ovariectomy in animals with an intact uterus. These findings suggest that some ovarian substance may be involved in the uterine regulation of the life span of corpora lutea.