The region of the murine major histocompatibility complex (MHC) between the Pb (A beta 3) and Ob (A beta 2) genes controls the expression of an intracellular complex named the LMP (low molecular weight polypeptide) complex. DNA probes for at least seven different genes mapping to this region were isolated. These hybridize to a minimum of eight different transcripts ranging from approximately 1.3 to 3.7 kilobases (kb). The deduced amino acid sequences of the corresponding cDNAs indicate that three of these genes are new members of the MHC class II gene family. These genes are transcribed in a tissue-specific pattern similar to that of the traditional class II genes. Two of the remaining four genes, HAM1 and HAM2, are homologous to one another and to a family of eukaryotic and prokaryotic transport proteins and may be involved in antigen processing. The tissue distribution of HAM1 transcripts is consistent with its proposed role in class I-restricted antigen processing, whereas HAM2 transcription appears more restricted and may be involved in antigen processing for class II-restricted T cells. The HAM2 gene may produce two differentially spliced transcripts. The identity of the remaining two genes is not known. Analyses of transcript sizes, tissue distribution, sequence, and genetic mapping data suggest that none of these genes code for LMP antigens.