The transepithelial transport of the angiotensin I-converting enzyme (ACE)-inhibitory and antihypertensive lactoferricin B (LfcinB)-derived hexapeptide LfcinB20-25 (RRWQWR) and of its two main fragments RWQ and WQ were investigated using a human intestinal cell (Caco-2) monolayer. The three peptides were susceptible to the action of brush-border peptidases. Intact LfcinB20-25 was not transported across Caco-2 whereas RWQ and WQ were both absorbed through the cell monolayer. Apparent permeability (Papp) values for absorptive transport across the monolayer were 0.7?¡Á?10?8?cm?s?1 (RWQ) and 3.9?¡Á?10?8?cm?s?1 (WQ). The effect of pathway-selective inhibitors on peptide absorption suggested paracellular diffusion as the main mechanism for the transport of intact RWQ and WQ. In?vitro incubation in human plasma showed half-life values of 1.9?min (RWQ) and 2.3?h (WQ). These results highlight the possibility of transport of antihypertensive lactoferricin B-derived peptides across human intestinal mucosa.