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Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the CNS thought to be due to an autoimmune response directed against myelin antigens. EAE is a commonly used animal model for MS and shares clinical, histopathologic and immunologic similarities with MS. Sex dimorphism has been well established in both MS and EAE. In MS, females are three times as likely as males to be affected; however male MS patients most commonly present with a more severe disease course with fewer effective treatments available. In EAE, certain mouse strains exhibit sex differences in response to myelin peptides. Sex-discrepant responses to disease have been attributed to sex and pregnancy hormones as well as genetics. Clinical trials are currently underway to investigate the role for sex hormones and multiple efforts are made to develop effective therapies to treat severe forms of chronic progressive MS. These studies have been aimed to investigate the impact of the pregnancy state on established EAE and to define the role of the PI3Kγ protein in immune-mediated protection from EAE disease. Profound suppression of the MS and EAE relapse rate is observed during late pregnanc