Alpha 1-antitrypsin is a serum protein commonly used as a marker of enteric protein loss. In this study, we have quantified alpha 1-antitrypsin concentration in human milk and its excretion by healthy term breast-fed infants. We found high concentrations of alpha 1-antitrypsin in early milk (0.3-0.6 mg/ml during the first week of lactation) while the concentration fell during subsequent weeks, being detectable through at least 3-4 months of lactation. Significant quantities of intact alpha 1-antitrypsin were found to be excreted by the breast-fed infants studied. The amount excreted was typically higher in early weeks (as much as 200 mg/24 h) and decreased with infant age, possibly due to both decreased intake from the milk as well as increased digestion of the protein by the maturing infant. In vitro studies demonstrated that the trypsin-alpha 1-antitrypsin complex resisted proteolysis by pepsin and pancreatic enzymes; thus, alpha 1-antitrypsin in milk can escape gastrointestinal degradation. We conclude that alpha 1-antitrypsin is not a suitable marker for intestinal protein loss by term breast-fed infants.