The H-2 complex has traditionally been interpreted as a maze of regions, subregions and loci coding for different traits. The two main theses presented here are, first, that a single H-2 locus is pleiomorphic in that it controls several functions such as allograft rejection, cell-mediated lymphocytotoxicity, mixed lymphocyte reaction, immune response, immune suppression and restriction of T-cell specificity; and second, that the physiological function of the H-2 complex is to guide T lymphocytes in their function of distinguishing self from non-self, and that all other H-2-controlled traits are artificial derivatives of this basic function. These two theses lead to a new, simplified interpretation of the H-2 complex.