Gastrointestinal loss of plasma is usually measured with radiolabeled macromolecules. These methods are expensive and cumbersome. The use of alpha 1-antitrypsin as an endogenous marker and the determination of alpha 1-antitrypsin fecal clearance enable the diagnosis of protein-losing enteropathy. alpha 1-Antitrypsin is measured in feces and blood by radial immunodiffusion, and the results are expressed as clearance. There is a significant correlation between alpha 1-antitrypsin fecal clearance and 51Cr-plasma protein clearance (r = 0.96, p less than 0.001). The sensibility of alpha 1-antitrypsin test compared to [51Cr] is 93.3%, the specificity is 90%. The positive predictive value is 97.7%, the negative predictive value 75%. We found no alpha 1-antitrypsin in gastric juice of pH below 3. In vitro studies confirmed the destruction of alpha 1-antitrypsin in gastric juice of pH below 3. There is a slight decrease of alpha 1-antitrypsin concentration when stools are incubated at 37 degrees C. In duodenal juice there is a small lessening of alpha 1-antitrypsin concentration after an incubation at 37 degrees C for 1 h. In conclusion, the fecal clearance of alpha 1-antitrypsin seems to be an inexpensive and quite reliable test of protein-losing enteropathy.