Various studies demonstrate that immunosuppression vis-à-vis paternal alloantigens may play a role for successful pregnancy. However, if this theory is true, the question that remains unanswered is how do syngeneic pregnancies manage to produce viable embryos. In allogeneic murine pregnancies immunosuppression is mediated by regulatory CD25(+)/Foxp3/CTLA-4 T cells. In order to evaluate whether these cells also play a role in syngeneic pregnancies, CD25(+)CD4(+) and CD25(+)CD8(+) were isolated from spleens of pregnant mice and examined as to the expression of specific suppressive and stimulatory markers, cytokine and soluble MHC class II antigen production. Interestingly, the CD25(+) cells and their products displayed an MHC-restricted stimulatory activity on total spleen cell proliferation assays. Although the CD25(+)CD4(+) and CD25(+)CD8(+) cells expressed Foxp3, they lacked CTLA-4, while expressing CD28. Non-specific proliferative effect was shown to be mediated by IL-3 and IL-4. The MHC-restricted proliferative effect; however, could be attributed to IA(d) molecules, which were detected in all culture supernatants of the T cell subpopulations tested and their elimination ablated the observed stimulatory activity. The detection of Ea, Eb1, Eb2 in addition to the Aa and Ab transcripts in these cells indicated the possible involvement of other class II gene combinations in this type of regulation. The results indicate that in the absence of paternal MHC alloantigens, maternal CD25(+) cells are involved in the development of immunostimulation to ensure foetal survival.