The human homeodomain protein EVX1 is a transcriptional repressor in transfected mammalian cells and this function depends on a region carboxyl-terminal to the homeodomain. In this study, we transiently expressed several deletions of the EVX1 C-terminal region in mammalian cells and investigated their effect on the transcription of a reporter gene directed by different promoters. We show that the repressor activity maps to a region of 51 amino acids with a high abundance of alanine and proline residues. This region is able to transfer the repressor function to either the entire HOXC6 or CREB transcription factors, or to the GAL4 DNA binding domain.