Genital tract epithelia regularly encounter and adapt to the existence of bacterial pathogens. This study provides evidence that the endocervical and ectocervical epithelia of the human female genital tract express bactericidal/permeability-increasing protein (BPI). The constitutive expression of BPI was restricted to cell-bound protein and unaffected by human papillomavirus type 16/E6E7 immortalization and proinflammatory cytokine stimulation. Epithelial BPI was, in part, responsible for killing a commensal strain of Escherichia coli. The results of the present study suggest that BPI is tightly regulated and functionally expressed by epithelial cells in the female reproductive tract and may play a role in regulating bacterial colonization in the genital mucosa.