Estrogens exert many of their behavioral effects by binding to nuclear estrogen receptor (ER) proteins, ERalpha and ERbeta. Recent studies involving ER knockout mice and selective ER agonists suggest that estradiol's anorexigenic effect is mediated via activation of ERalpha. To investigate this hypothesis, we examined whether the presumptive ERalpha antagonist, MPP, could block estradiol's anorexigenic effect. In the first series of experiments, the effects of MPP on food intake and uterine weight were monitored in ovariectomized (OVX) rats treated with either a physiological dose of estradiol benzoate (EB) or a selective ERalpha agonist (PPT). In the final experiment, food intake was monitored following acute administration of MPP in ovarian-intact (cycling) female rats. Contrary to our hypothesis, MPP failed to attenuate either EB's or PPT's ability to decrease food intake and increase uterine weight in OVX rats. However, in ovarian-intact rats, a similar regimen of MPP treatment attenuated the phasic decrease in food intake that is associated with estrus. We conclude that MPP may be a useful tool to investigate the behavioral actions of endogenous estradiol, but may have limited utility in studying the behavioral effects of exogenous estradiol in OVX rats.