Zinc finger genes encode proteins containing tandemly repeated zinc-mediated folded structures that are found in several transcriptional regulatory proteins. To identify new zinc finger genes, we have screened at low stringency human cosmid libraries enriched in chromosome 22 sequences with a probe derived from the finger region of the mouse Kruppel-like gene, mKr2. We identified 23 nonoverlapping human cosmids cross-hybridizing with the probe. All sequences obtained from cosmid subclones hybridizing with the probe revealed Kruppel-type consensus sequences. Hybridizations to somatic cell hybrid panels and to metaphase chromosomes revealed that 2 nonoverlapping zinc finger cosmids map to chromosome 22p and 4 map to 22q11.2. The 17 other nonoverlapping cosmids most likely map to other chromosomes. The short arms of acrocentric chromosomes are thought to encode only ribosomal RNA genes. Therefore, the identification of two zinc finger genes on chromosome 22p represents an unexpected finding of unknown significance. The four zinc finger genes that map to 22q11.2 are within the cat eye and DiGeorge syndrome regions and thus provide us with potential candidate genes for these developmental malformations.