The I-E and I-C subregion products have been identified specifically in haplotypes H-2k and H-2d. Haplotypes H-2p and H-2r are assumed to express products of I-E/I-C subregion on the basis of cross-reactions with anti-I-Ek sera. Anti-I-Ek or I-Ed sera do not cross-react with haplotypes H-2s, H-2b, H-2q, and H-2f. Specific immunizations to produce anti-I-Eb and anti-I-Es alloantisera have been unsuccessful. We turned to xenoimmunization to serologically identify the gene products of this chromosomal segment in the above haplotypes. NP-40 detergent solubilized antigenic material mixed in Freund's complete adjuvant were immunized into rabbits. Two weeks later a booster was given and the rabbits bled one week later for antisera analyses. The rabbits were then boosted once a month and bled periodically. The rabbit antiserum reacted with all mouse strains. Absorptions with appropriate recombinants showed the presence of specific antibodies against the I region products.