We have previously shown that the human genome includes hundreds of genes coding for putative factors related to the Krüppel zinc-finger protein, which regulates Drosophila segmentation. We report herein that about one-third of these genes code for proteins that share a very conserved region of about 75 amino acids in their N-terminal nonfinger portion. Homologous regions are found in a number of previously described finger proteins, including mouse Zfp-1 and Xenopus Xfin. We named this region the Krüppel-associated box (KRAB). This domain has the potential to form two amphipathic alpha-helices. Southern blot analysis of "zoo" blots suggests that the Krüppel-associated box is highly conserved during evolution. Northern blot analysis shows that these genes are expressed in most adult tissues and are down-regulated during in vitro terminal differentiation of human myeloid cells.