Bactericidal/permeability-increasing protein (BPI), a cationic protein present in the azurophilic granule and on the surface of polymorphonuclear leukocytes, specifically interacts with lipopolysaccharide (LPS). This study demonstrates for the first time, using flow cytometry with specific anti-BPI monoclonal antibody (MAb), that human peripheral blood monocytes express BPI on their cell surface. The monocyte cell surface BPI was shown to bind to LPS, because binding of anti-BPI MAb 4E3 (which is known not to react with BPI to which LPS is bound) to cell surface BPI was strongly reduced after preincubation of cells with LPS. However, cell surface BPI did not quantitatively contribute to the interaction of LPS with the monocyte cell membrane, since preincubation of cells with 4E3 did not block binding of LPS-fluorescein isothiocyanate to monocytes. The origin of the monocyte cell surface BPI remains to be further elucidated.