When is a sex diVerence not a sex diVerence?

Brain sexual diVerentiation in mammals requires activity of gonadal hormones; organizational eVects of these steroids on brain development occur early in life while activational ones in adulthood ensure appropriate and timely sex-speciWc behaviors. This traditional view has long served as a reliable model for sexual diVerentiation of reproductively relevant brain structures. Here, we take a fresh look at this model but refocused in the context of sexual diVerentiation of non-reproductive parameters and with an emphasis on the hippocampus, a telencephalic brain structure predominantly involved in cognition and stress regulation. We explore sex diVerences in morphology, neurochemistry, and hippocampal-dependent behaviors to propose a new prototype that can be used to explain and further investigate the eVects of steroid hormones, those synthesized gonadally or intracerebrally, on hippocampal development and function. We also propose that a new vernacular be employed, one that distinguishes hormonally modulated responses from sex diVerences, and argue these are mechanistically and functionally distinct. Understanding when and how the sexes are diVerent is as important as understanding when and how they are the same, at the biological, social, and cultural level.  2005 Elsevier Inc. All rights reserved.