The first viable interspecific chimeras in mammals have been made by mixing embryonic cells from two species of mouse, Mus musculus and Mus caroli. These chimeras resemble intraspecific chimeras in M. musculus in their patterns of mosaicism. They provide an interesting experimental system for studying interactions between cells of the two species. Three separate but related areas of investigation utilizing these chimeras are described. 1) In situ DNA-DNA hybridization using a cloned repetitive DNa sequence from M. musculus has enabled M. caroli and M. musculus cells to be distinguished in bone marrow spreads from chimeras. Further refinement of this technique should allow use of this in situ marker system for detailed analysis of cell distribution in chimeras. Such a ubiquitous marker system is not yet available in M. musculus. 2) Breeding interspecific chimeras has increased production of interspecific hybrids, which are very useful for studies of genetic interactions between the two species. 3) Mus caroli embryonic cells can survive in the M. musculus uterus in a chimera, although M. caroli embryos alone die around d 11 to 16 of pregnancy in M. musculus. Investigation of this phenomenon has implicated immune effector mechanisms in death of M. caroli embryos and has revealed the importance of trophoblast genotype for survival of foreign cells in the uterine environment.