Mhc genes in the chicken and at least some other gallinaceous birds are organized into genetically independent clusters containing both class I and class II genes. The genes within these clusters are of interest in that they may provide insights into the function and evolution of the Mhc not found previously in the mammalian paradigms. In the chicken the two gene clusters called B and Rfp-Y reside on the same chromosome but are separated by a region supporting highly frequent meiotic recombination such that B and Rfp-Y haplotypes are inherited independently. Genes within Rfp-Y are apparently transcriptionally active but whether any class I molecules encoded within Rfp-Y present peptides in the fashion of classical class I molecules or perform more specialized functions has not been determined. Consistent with the capacity to hybridize under highly stringent conditions with B system class I DNA probes, the Rfp-Y class I loci are about 73% identical in coding region sequence with the classical class I genes located in the B system. At least one Rfp-Y class I locus is transcribed in nearly all organs and exhibits allelic sequence diversity similar to that of classical class I genes. These similarities suggest that the Rfp-Y class I molecules could be functionally nearly identical to their classical B system counterparts. However, distinctive substitutions of residues that are highly conserved in the peptide binding groove of classical molecules occur in the Rfp-Y encoded molecules making it unlikely that they are capable of presenting antigen in the manner of classical class I molecules. This observation together with those made previously for Rfp-Y class II loci demonstrate that the Rfp-Y gene cluster likely represents specialization not previously encountered in the study of Mhc evolution.