The Pleisl locus was isolated as a common site of viral integration involved in myeloid leukemia in BXH-2 mice. Meisl encodes a novel homeobox protein belonging to the TALE (three amino acid loop extension) family of homeodomain-containing proteins. The homeodomain of Meisl is the only known motif within the entire 3?O-amino-acid protein. Southern blot analyses using the Meisl homeodomain as a probe revealed the existence of a family of Meisl-related genes (Mrgs) in several diverged species, in addition, the 3' untranslated region (UTR) of Meisl was remarkably conserved in evolution. To gain a further understanding of the role lqeisl plays in leukemia and development, as well as to identify conserved regions of the protein that might reveal function, we cloned and characterized lqrgs from the mouse and human genomes. We report the sequence of Mrgl and IqR62 as well as their chromosomal locations in murine and human genomes. Both Plrgs share a high degree of sequence identity with the protein coding region of Meisl. We have also cloned the Xenopus laevis ortholog of Meisl (XMeisl). Sequence comparison of the murine and Xenopus clones reveals that lqeisl is highly conserved throughout its coding sequence as well as the 3' UTR. Finally, comparison of Meisl and the closely related Mrgs to known homeoproteins suggests that lqeisl represents a new subfamily of TALE homeobox genes.