Part of the mechanism through which estradiol, acting via estrogen receptor- (ER) signalling, inhibits feeding in rats and mice is increasing the satiating potency of cholecystokinin (CCK) acting on peripheral CCK-1 receptors. Ingested lipid is a principal secretagogue of intestinal CCK, and intraduodenal lipid infusions elicit CCK-mediated satiation in animals and humans. Here we tested whether estradiol affects the satiating potency of intraduodenal lipid infusions in ovariectomized (OVX) rats and, using c-Fos immunocytochemistry, searched for potential brain sites of ER involved. Food-deprived OVX rats with open gastric cannulas sham fed 0.8 M sucrose 2 days after estradiol (estradiol benzoate, 10 µg, sc) or vehicle injection. Estradiol markedly increased the satiating potency of intraduodenal infusions of Intralipid, but not the satiating potency of L-phenylalanine (10 min infusions, 0.44 ml/min, 0.13 kcal/ml), which in male rats satiates via a CCK-independent mechanism. Estradiol had no significant effect in rats pre-treated with the CCK-1 receptor antagonist Devazepide (1 mg/kg, ip). The effect of estradiol on intraduodenal Intralipid-induced satiation was mirrored by selective increases in the number of cells expressing c-Fos immunoreactivity in a circumscribed region of the nucleus tractus solitarius, just caudal to the area postrema (cNTS), but not elsewhere in the NTS or in the hypothalamic paraventricular or arcuate nuclei. In addition, a significant proportion of cNTS c-Fos positive cells also expressed ER. These data provide behavioral and cellular evidence that estradiol-ER signaling in cNTS neurons increase the satiating potency of endogenous CCK released in response to ingested lipid.