We recently reported the isolation of human beta-defensin-2 (hBD-2), a novel epithelia-derived peptide antibiotic belonging to the beta-defensin family. hBD-2 is expressed in skin and epithelia of the airway system, where it is believed to contribute to its antimicrobial defense. By fluorescence in situ hybridization using a hBD-2 genomic DNA probe and subsequent fluorescence R-banding, the hBD-2 gene (HGMW-approved symbol DEFB2) was assigned to human chromosome region 8p22-p23.1. PCR with a set of CEPH YAC clones spanning this chromosomal region revealed CEPH YACs 773G4, 920D12, and 820B4 to contain the hBD-2 gene. Relying on the preexisting physical maps of 8p22-p23.1, the hBD-2 gene was mapped in close proximity to D8S1993 (WI-9956) within the interval flanked by D8S552 and D8S1130 (CHLC.GATA25C10). The fact that all currently described genes encoding defensins map to chromosome 8p21-pter suggests that a gene cluster in this chromosomal region may play a major role in antimicrobial defense.