Proteasomes are the multisubunit protease involved in the generation of peptides presented by MHC class I molecules. When cells are stimulated with IFN-gamma, two MHC-encoded subunits, low Mr polypeptide 2 (LMP2) and LMP7, are incorporated into the proteasomal complex by displacing the housekeeping subunits, designated Y and X, respectively. Recent evidence indicates that besides the LMP2/Y and LMP7/X subunits, there is another pair of structurally similar beta-type subunits, designated MECL1 and Z, whose expression is regulated reciprocally by IFN-y. In the present study we determined the genomic organizations of the mouse genes, Psmb10 and Psmb7, that encode the MECL1 and Z subunits, respectively. Although the two genes differ > 10-fold in size, they both have eight exons, with the exon-intron boundaries located precisely at the equivalent positions. The organization of the Psmb10 and Psmb7 genes differs from those of the genes encoding the other two pairs of IFN-gamma-regulated subunits. Thus, comparison of the gene structures supports the idea that Psmb10 and Psmb7 arose by duplication from an immediate common ancestor. The promoter region of the Psmb10 gene contains two IFN-stimulated response elements, the functionality of which was confirmed by in vitro mutagenesis. The mouse Psmb10 gene maps to chromosome 8, thus outside the MHC like its human counterpart. Besides the Psmb7 gene previously mapped to chromosome 2, a truncated processed pseudogene, designated Psmb7-ps, was identified and mapped to chromosome X.