Senile changes in the pattern of the estrous cycles were analysed in various inbred strains of mice. Estrous symptoms in old female mice were ascribed to ovarian hormone production. However, the sensitivity of old animals to intravaginal as well as subcutaneous administration of estrone was considerably decreased. Cyclic estrous changes of the vaginal smears may continue up to a very great age, while a gradual decrease of the estrous cycles occurs towards the end of life. There were considerable strain differences. DBAf mice finally became anestrous. This condition was apparently related to amyloid infiltration and cystic degeneration of the ovaries. C57BL mice, on the other hand, underwent a continuous estrogenic stimulation in old age. This was related to the accumulation in the ovaries of large masses of lutein-like interstital cells. The involutionary changes in old mouse ovaries were accompanied by the occurrence of new cell proliferations which were derived from germinal epithelium and from the tubules of the rete ovarii. These cells had the appearance of granulosa cells and formed anovular follicles similar to those occurring in mouse ovaries under experimental conditions.