IkappaBalpha belongs to a gene family whose members are characterized by their 6-7 Ankyrin repeats, which allow them to interact with members of the Rel family of transcription factors. We have sequenced a human IkappaBalpha genomic clone to determine its gene structure. The human IkappaBalpha gene (IKBA) has six exons and five introns that span approximately 3.5 kb. This genomic organization is similar to that of other members of the Ankyrin gene family. The human IKBA gene shares similar intron/exon boundaries with the human BCL3 and NFKB2 genes, which is consistent with their conserved Ankyrin repeats. To examine further the evolutionary relationship between human IkappaBalpha and other members of its gene family, we performed a phylogenetic analysis. Although the resulting phylogenetic tree does not identify a common ancestor of the IkappaBalpha and other members of its gene family, it indicates that this family diverges into two groups based on structure and function.