A wealth of information has been published on the effect of stress on the nervous, endocrine and immune systems during the past two decades. Further, stress is known to be abortogenic in murine and human pregnancies. It is logical to suspect that stress might cause abortion by altering the endocrine and/or immune system, and thus leading to a hampered or failing pregnancy maintenance. Lowered levels of progesterone did indeed occur as a result of stress and there was little change in cortisol or prolactin. Adequate levels of progesterone exert an antiabortive effect by induction of a Th2 biased immune response an by controlling NK activity. In stressed mice, increased levels of the abortogenic cytokine TNF-α, IFN-γ and IL-12 were found in decidua in early pregnancy and this was associated with decreased levels of pregnancy-protective TGF-β2-related suppressive activity in uterine decidua later in pregnancy. Interestingly, the progesterone derivative dydrogesterone abrogates stress triggered abortion by inducing a Th2 biased local immune response. In summary, the current study represents an important step towards bridging the longstanding assumption of vaguely defined negative effects of stress on pregnancy outcome with the mainstream of current endocrine-immunological research by showing that stress may indeed influence pregnancy outcome along a putative ‘brain decidua axis’.