The primary structures of α and β chains from both I-A and I-E/C subregions of several haplotypes were exchange chromatography of tryptic peptides. The materials examined were obtained from NP-40 extracts of biosynthetically radiolabeled normal spleen cells. The preparations were subjected to LcH-Sepharose affinity chromatography prior to immunoprecipitation with specific alloantisera; α and β chains were separated by polyacrylamide gel electrophoresis and/or hydroxylapatite chromatography in SDS. Comparative chromatographies of tryptic peptides from α and β chains reveal that corresponding chains from the highly cross-reactive I-Ak and I-Ar gene products share approximately 65–75% of their peptides. Preliminary results suggest that for the I-E/Ck and I-E/Cr products the α chains share all peptides, whereas the β chains share only 65% of their peptides. This latter result, considered in light of the proposed assignment of Ia.7 to the I-E subregion (David and Cullen, in press), suggests that the I-Ek specificity Ia.22 (which I-Er lacks) may be carried specifically on the Eβk chain.