Women with multiple sclerosis (MS) often experience a decrease in relapse rate during pregnancy, most notably during the third trimester, with a flare of disease activity 3-6 mo postpartum. Studies in experimental autoimmune encephalomyelitis (EAE), an animal model for MS, have shown that pregnancy delays the onset and decreases the incidence of disease. We investigated the effect of pregnancy and the postpartum period in a remitting-relapsing model of murine EAE. When immunization occurs during pregnancy, mice show a reduction in the incidence of EAE as well as a decrease in clinical severity, while mice immunized during the postpartum period exhibit more severe disease. No differences in lymphocyte proliferation or expression of activation markers were noted when immunization occurred during pregnancy as compared with the nonpregnant controls. Mice immunized during pregnancy produced less TNF-alpha and IL-17, and showed an increased number of IL-10-secreting cells within the CD11b+, CD11c+, CD19+, and CD4+/CD25+ populations. No differences were noted in the production of IFN-gamma, IL-2, IL-4, and IL-5. These results suggest that when an Ag is introduced during pregnancy, an immunoregulatory rather than an immunosuppressive or Th2 environment predominates.