The cysteine-rich beta-defensin peptides are broad-spectrum bactericidal agents expressed in epithelial and myeloid tissues. The human beta-defensin-1 (hBD-1) gene maps adjacent to the human alpha-defensin cluster and is expressed in the respiratory, gastrointestinal and genitourinary tracts. Here, we characterize a mouse beta-defensin gene (mBD-1) which is: (1) closely related to hBD-1 both in sequence and gene organization; (2) expressed at high levels in the mouse kidney and at lower levels in brain, heart, lung, uterus, spleen, skeletal muscle, stomach, and small intestine; and (3) maps to mouse chromosome 8 at or near the location of the mouse alpha-defensin genes. These data indicate that mBD-1 is a close homolog of hBD-1, and suggest that analysis of its role in mouse host defense may provide significant insights into human epithelial innate immunity.