Lactoferrin (LF), a glycoprotein present in milk and other secretions, may provide a nutritional ingredient for the treatment of intestinal disorders associated with hyperpermeability, oxidative stress and inflammation. The aim of the study was to determine the survival rate of orally administered recombinant human lactoferrin (rhLF) in the upper gastrointestinal (GI) tract and in the small intestine in vivo in humans. Female ileostomy patients [n = 8; median age 44 (43-57) y] ingested a test beverage containing 5 g rhLF and collected full ileostomy output for 24 h. The passage of the test beverage was monitored using radio-opaque markers. Intact LF in ileal effluent was quantified by ELISA. The entire test beverage passed the small bowel during the 24-h ileal effluent collection period. LF was excreted at a low but constant rate [0.35 (0.28-0.47) micro g LF/2 h]. Gastrointestinal passage of the test beverage and LF excretion over time in the ileal effluent were not correlated. In total, a median of 4 micro g LF was excreted over the 24-h collection period, whereas 5 g rhLF was ingested. Hence, dietary rhLF is digested in the upper GI tract and does not reach the colon. Intact LF appearing in ileostomy effluent is likely to originate from an endogenous source.