By presenting antigenic peptides to T lymphocytes, major histocompatibility complex (MHC) class I molecules play important roles in the human immune system. Knowledge is limited on the evolutionary history of human MHC class I-related molecules. An expressed class I gene, MRI, has now been identified on human chromosome 1q25, outside the MHC. In contrast to other known human divergent class I genes, MR1 encodes peptide-binding domains similar to those encoded by human leukocyte antigen (HLA) class I genes on chromosome 6 and by nonmammalian classical MHC class I genes. This gene may thus contribute to understanding the evolution of the MHC.