To contribute to the isolation of genes within the q-24-qter region of the human X chromosome,we screened three cDNA libraries (human fetal brain, liver and skeletal muscle) with a cosmid clone containing a CpG island previously mapped in the q28 region. A full-length 2.1-kb cDNA clone was isolated (XIB); DNA databank searches revealed identity with an EST fragment (XAP-1), residing between the RCP/GCP and G6PD loci. The XIB coding region (909 bp) showed 44% amino acid (aa) identity to pig DNase I. Several conserved residues have been observed between these two genes including aa in the active site. XIB expressed a single transcript in adult heart and skeletal muscle, whereas, in some fetal tissues, two different-sized transcripts were seen. Zoo blot analysis showed a remarkable cross-species conservation. Expression and sequence of this novel gene are reported.