Abstract Fecal clearance of plasma α 1-antitrypsin is used as a measure of protein leakage into the intestinal tract. In this study, the α 1-antitrypsin concentration in stool and the plasma clearance of α 1-antitrypsin in normal subjects and in a consecutive series of patients with chronic diarrhea, malabsorption, or unexplained hypoalbuminemia was determined. The normal subjects were studied in their usual state and also when they had diarrhea secondary to ingestion of lactulose, sorbitol, sodium sulfate, or phenolphthalein. The study first concluded that induced diarrhea can cause an increase in α 1-antitrypsin clearance; if this is not considered in establishing normal values, there may be an overdiagnosis of excess protein leakage in patients with diarrhea. Second, there is a highly significant statistical correlation ( P < 0.001) between α 1-antitrypsin clearance and serum albumin concentration. On average, the serum albumin falls below 3.0 g/dL (30 g/L) when the α 1-antitrypsin clearance exceeds 180 ml/day, a value that is about threefold higher than the upper limit of normal. Third, three of nine patients with microscopic/collagenous colitis had elevated clearance of α 1-antitrypsin; by contrast, abnormal α 1-antitrypsin clearance was not found in 23 patients with idiopathic secretory diarrhea. Fourth, fecal α 1-antitrypsin concentration is not a reliable index of abnormal α 1-antitrypsin clearance.