The mouse isoantigens determined at the major histocompatibility locus known as H-2 have been found to be closely associated with the cellular surface membranes, with the membranes of the endoplasmic reticulum, and probably with those of the lysosomes as well. Mitochondrial membranes, on the other hand, show little or no H-2 antigen activity. Membrane material prepared from certain tissues, including brain and muscle, have no detectable H-2 antigenic activity. Evidence is presented which indicates that all of the H-2 antigens of the genome are expressed as a unit, supporting the hypothesis that the complex H-2 genetic locus consists of a single cistron. It is postulated that these histocompatibility antigens form some structural or functional unit in the membranes of cells.