CONTEXT: Estrogen receptor α (ERα) in the ventromedial (VMN) and arcuate (ARC) nuclei of female rodent mediobasal hypothalami (MBHs) provides a crucial molecular gateway facilitating estradiol (E OBJECTIVE: We hypothesized that knockdown (KD) of ERα expression in the hypothalamic VMN and ARC of female marmosets would diminish sexual receptivity, while simultaneously disrupting gonadotropic and metabolic homeostasis. METHODS: We ovariectomized (OVX) adult female marmosets of comparable age and weight, immediately replaced E RESULTS: ERα expression was significantly diminished in the VMN and ARC, but not the preoptic area (POA), of ERαKD females coincident with elimination of timely female sexual responses, more than 80% loss of female receptivity, modestly elevated gonadotropin levels, hyperglycemia, and diminished calorie consumption. Density and intensity of ERα-expressing cells in the VMN correlated positively with female sexual receptivity and calorie consumption, negatively with timeliness of female sexual responses, and in the ARC, correlated negatively with calorie consumption. CONCLUSION: ERα activation in the female NHP MBH is critically important for female sexual behavior and modestly contributes to gonadotropic and metabolic control.