Parthenogenesis is the process in which an oocyte develops into an embryo without fertilization. Parthenogenetic activation can be performed at various stages of meiosis, yielding embryos with distinct genetic patterns of homozygosity and heterozygosity. Parthenogenetic embryonic stem (pES) cells derived from such embryos have heterozygous patterns that can be identified using genome-wide single nucleotide polymorphism (SNP) analysis, to determine whether extrusion of the first or second polar body has been inhibited. Heterozygous pES cells carrying the full complement of major histocompatibility complex (MHC) antigens matched to the oocyte donor may provide a potential source of immunematched cells and tissues for cell replacement therapy. In this review, we summarize the process of deriving heterozygous MHC-matched pES cells using mouse and human models.