The mouse Lmp-2 gene is located within the major histocompatibility complex (MHC) class II region and encodes a subunit of the 20S cytosolic proteasome. Previous studies indicated that the 20S proteasome is a catalytic core of the 26S proteolytic complex that possesses a latent multicatalytic proteinase activity and catalyzes an ATP-dependent, selective breakdown of proteins ligated to ubiquitin. This complex has recently been postulated to be involved in the processing of endogenous antigenic peptides for the MHC class I pathway. Here, we report the genomic organization and tissue expression of the mouse Lmp-2 gene. We have cloned and sequenced the entire mouse Lmp-2 gene, including 5'- and 3'-flanking regions. The gene consists of six exons, and its genomic organization is very similar to that of the recently described human LMP2 gene. Putative promoter and enhancer elements were identified in the 5'-flanking region by sequence comparison with known consensus sequences. The Lmp-2 gene is expressed in most tissues of unstimulated mice, except for brain tissue. The comparison of the 5'-flanking region of human and mouse sequences is discussed.