At least 110 genes are now known to be located in the 4000 kb of DNA encompassing the human major histocompatibility complex (MHC) in the chromosome band 6p21.3. Recent genomic sequence analysis of a 90 kb segment of DNA containing the tumour necrosis factor genes in the class III region of the MHC has predicted the presence of three potential exons mapping between the BAT1 and TNFB genes (12). A near full-length cDNA clone corresponding to a novel gene located between BAT1 and TNFB that contains sequence corresponding to one of these putative exons, has been isolated from a premonocytic leukaemic cell line cDNA library. Characterization of this gene reveals that it spans 13.5 kb of DNA, with the 3' end of the gene lying approximately 12 kb from the 5' end of the TNFB gene. The cDNA hybridizes to a approximately 1.6 kb mRNA in a number of different cell types, including monocytes, T cells, B cells and hepatocytes. The putative polypeptide encoded by this cDNA is 381 amino acids in length, with a non-glycosylated M(r) of 43214. It contains one partial and two full ANK repeats, which bear a marked similarity to those in the I kappa B family of proteins, suggesting that the protein encoded by the novel gene could represent a divergent member of this family.