Background:Fecal α1-antitrypsin is used as a marker for intestinal protein loss reflecting increased intestinal permeability. Exact data of fecal α1-antitrypsin in newborn infants are not available.Methods:30 healthy mature neonates and three infants with impaired gastrointestinal passage due to stenoses and atresia respectively, were investigated during the first days of life. The amniotic fluid of 13 and the serum of 17 infants was available. α1-antitrypsin was determined using the radial immunodiffusion method.Results:Normal newborns showed mean fecal α1-antitrypsin levels (±SD) of 2061 ± 817 mg/dl (day 1), 1186 ± 720 mg/dl (day 2), 308 ± 380 (day 3), 35 ± 27 (day 5), and 27 ± 21 mg/dl (day 6). Two infants with esophageal atresia presented a much lower pattern, and one with annular pancreas had a fecal α1-antitrypsin pattern comparable with that of normal babies. Serum α1-antitrypsin was normal (275 ± 52 mg/dl), and amniotic fluid contained 20 ± 12 mg/dl α1-antitrypsin.Conclusions:The pattern of neonatal fecal α1-antitrypsin content appears to reflect the meconium clearance of the gut rather than intestinal permeability and “gut closure.” We hypothesize that the origin of increased fecal α1-antitrypsin is the result of accumulated secretions from bile, the pancreas, and the duodenum, but α1-antitrypsin originating from swallowed amniotic fluid during pregnancy may play an additional role.