Numerous studies have suggested that estradiol (E) improves spatial memory as female rats with E perform better than those without E. However there is an inverse relationship between E and luteinizing hormone (LH) levels and LH could play a role. We examined whether treatment with the LH homologue human chorionic gonadotropin (hCG), would impair spatial memory of adult E-treated female rats. In the object location memory task, ovariectomized (ovxed) rats treated with E and either a single high dose (400 IU/kg) or a lower repeated dose of hCG (75 IU/kg hourly for 8 h) showed spatial memory disruption compared to ovxed rats treated with estradiol alone. Impairment was attributed to memory disruption as performance improved with shortened delay between task exposure and testing. Tests on another spatial memory task, the Barnes maze, confirmed that hCG (400 IU/kg) can impair memory: although E+veh treated animals made significantly fewer hole errors across time, E+hCG-treated did not. In humans, high LH levels have been correlated with Alzheimer's disease (AD). Because brain amyloid-beta (Abeta) species have been implicated as a toxic factor thought to cause memory loss in AD, we analyzed whether hCG-treated animals had increased Abeta levels. Levels of Abeta from whole brains or hippocampi were assessed by Western blot. hCG treatment to E-implanted females significantly increased soluble Abeta40 and Abeta42 levels. These results indicate that high levels of LH/hCG can impair spatial memory, and an increase in brain Abeta species may account for the memory impairment in hCG-treated rats.