The gene on chromosome 12 coding for the human protein HMGI-C has been cloned and partially sequenced. It consists of five exons, the first and last of which include long untranslated regions. The 5' UTR includes a (CA/T)n tract and a polymorphic (CT)n tract. Exons II, III and IV (87, 51 and 33 bp) are dispersed over > 30 kb. Exons I-III separately encode the three basic DNA binding domains ('A-T hooks'), exon IV encodes an 11 amino acid sequence characteristic of HMGI-C and absent from the human HMGI(Y) gene [Friedmann, M., Holth, L. T., Zoghbi, H. Y. and Reeves, R. (1993) Nucleic Acids Res., 21, 4259-4267], whilst exon V encodes the acidic C-terminal domain, which is subject to multiple phosphorylation. The HMGI-C gene is thus a striking example of the separation of functional protein elements into different coding exons.