Mouse embryos which are homozygous for the t12 mutation die at the late morula stage whereas those that are homozygous for the t6 mutation die at either the early or the late egg cylinder stage. The phenotypic expressions of these genotypes include the lack of trophectoderm formation (t12/t12 embryos) and its subsequent differentiation (t6/t6 embryos). In the latter embryos, the trophectoderm cells do not transform into giant cells. The exact cause(s) of these phenotypic expressions is not known. Nor is it known if the defects are caused by the recessive lethal T haplotypes or their linked, unique H-2 haplotypes. A means for distinguishing the effect of the T haplotype from that of the unique H-2 haplotype on early embryogenesis is to microinject overlapping sequences of wild-type DNA covering either the T haplotype region or the H-2 haplotype region into homozygous mutant zygotes and determine which sequence(s) partially or totally rescues the homozygous T embryos. In the proposed series of experiments we will inject t12/t12 and t6/t6 zygotes with overlapping sequences of wild-type H-2 DNA and then follow their subsequent development both in vitro and in vivo. Positive results from these studies will define the role of the wild-type H-2 locus in early mammalian embryogenesis and in the formation of the trophectoderm and its derivatives.