Although the mechanisms by which the fetal allograft escapes rejection are still poorly understood, abundant evidence has accumulated suggesting multiple roles for major histocompatibility complex (MHC) genes in pregnancy. Specific maternal MHC genotypes and maternal-fetal histocompatibility have been associated with recurrent spontaneous abortion, decreased fecundity, segregation distortions, altered sex ratios, fetal growth rates, and maternal autoimmune disease progression. In this review, the evidence for a variety of MHC gene effects in human pregnancy is considered.