Pregnancy outcome may be altered by both genetic and environmental factors. The mating of CBA/J female mice with DBA/2 males normally results in pregnancies characterized by a relatively high incidence of early embryo loss compared with most other syngeneic or allogeneic matings. This study addressed the role of normal laboratory stress in the induction of early embryo loss. The previously studied 'Bruce effect' describes the total loss of preimplantation embryos (pregnancy block) that is apparently caused by the stress induced by the presence of an alien male and mediated by neuroimmunological effects on prolactin activity. To determine whether this effect could be responsible for the high incidence of postimplantation embryo losses in the CBA/J × DBA/2 model, the original DBA/2 male was replaced on day 6 of gestation by another DBA/2 male, a CBA/J, a C57Bl/6 or a BALB/c male. The relatively high incidence of embryo loss was not affected by removing the original DBA/2 male or introducing another DBA/2 or a CBA/J male, indicating that stress induced by an alien male did not increase the postimplantation losses in this model. Furthermore, the introduction of a DBA/2 male to a CBA/J female that had been mated with a BALB/c male did not elicit early embryo loss. However, the replacement of the original DBA/2 male by a BALB/c male dramatically reduced the incidence of early embryo loss in pregnant CBA/J female mice. The introduction of a C57Bl/6 male also reduced embryo loss but to a lesser extent. Furthermore, this effect was shown to be independent of the testes and was induced by factors present in the bedding from cages in which BALB/c male mice had been housed. The presence of the BALB/c male in the cage with the pregnant CBA/J female resulted in a significant reduction in the infiltration of uterine implantation sites by maternal macrophages, coincident with a reduction in early embryo losses. These studies therefore show that the maternal cell-mediated immune response in the uterus to the fetal graft is altered, apparently by pheromonal messages derived from the resident male. The introduction of an alien BALB/c male to a pregnant CBA/J female after implantation of CBA/J × DBA/2 embryos had occurred, while unable to alter the fetal genotype, apparently altered the maternal uterine cellular response and had a profound effect on pregnancy outcome.