A new genetic region, mapping within the H-2 complex, has been serologically defined with several alloantisera raised in mice which differ at the D region. When these antisera were absorbed to remove H-2D antibodies, residual antibody activity remained that reacted in a strain-specific manner, and the antigens involved mapped to a new genetic region between the S and D regions. Two allelic variants relating to the d and k haplotypes have been defined by genetic mapping studies. This new region has been designated H-2U and the antigens it controls appear to resemble Ia antigens in their cellular distribution and molecular weight. The new antigen is primarily expressed on B cells, and is carried on protein molecules having approximate molecular weights of 36 000 and 60 000 daltons and resembling the alpha and alpha--beta chain dimer characteristic of Ia antigens.