We previously reported the identification of a novel candidate proto-oncogene involved in the translocation t(14;19)(q32;q13) found in some cases of human B-cell chronic lymphocytic leukemia. This gene, BCL3, is a member of the I kappa B family, whose encoded proteins regulate the NF-kappa B family of transcription factors. Here we describe the genomic structure of BCL3. The gene contains nine exons, spanning 11.5 kb. In comparison to other members of the I kappa B family, there is a remarkable conservation of the exon-intron boundaries in relation to the coding sequences, consistent with an origin from a common ancestral gene. BCL3 is unusual in containing two CpG islands, a 5' island encompassing the first exon, the other lying within the gene. Southern blot analysis using methylation-sensitive restriction enzymes revealed that while the 5' CpG is unmethylated in all tissues tested, the degree of methylation of the internal CpG island varies.