Young adult cyclic female rats were each injected with 2 mg estradiol valerate (EV) in sesame oil. Controls received an equivalent volume of sesame oil. Within 2 months after injection, most of the EV-treated animals showed persistent vaginal estrus and small polyfollicular ovaries as well as pathological changes in the hypothalamic arcuate nucleus. This pathological process was gradually progressive such that by 6 months after EV injection, the basal lateral region of the nucleus contained numerous reactive microglia, astrocytes, and degenerating elements of the neuropil. The experimental rats had elevated plasma PRL and GH concentrations which gradually diminished. Plasma estradiol concentration remained elevated 2 months after injection, while plasma LH and FSH concentrations stayed within the high and low normal range, respectively. The pituitary glands of injected animals weighed significantly more than those of controls 5.5 months after injection, but the enlarged glands did not cause hypothalamic compression. As mechanical anterior deafferentation of the medial basal hypothalamus has previously been shown to produce similar endocrine and reproductive alterations, it may be that estradiol treatment results in a functional-anatomical disconnection of the arcuate nucleus from the more anterior hypothalamic areas that regulate cyclicity. Whether this type of functional-anatomical phenomenon underlies other varieties of induced or secondary acyclicity in females remains to be determined.