The chromosomal localization of 17 human homeoboxes and the predicted primary sequence of the encoded homeodomains is reported. These homeoboxes are clustered in four complex HOX loci on chromosomes 2, 7, 12 and 17. Although the identification of human homeoboxes has not been completed, existing data permit preliminary conclusions on the origin and evolution of these complex loci to be drawn. The homeo-domains of one HOX locus can be unambiguously aligned to the homeodomains of the other HOX loci, so that corresponding homeodomains in all loci can share the maximal peptide sequence identity. This one-to-one correspondence of individual homeodomains in different chromosomal loci suggests the hypothesis of large-scale duplications of a single complex locus and subsequent spreading in different chromosomes. The existence of an ancestral complex locus might have predated the divergence of the arthropod/annelid and vertebrate evolutive lineages.