We evaluated fecal clearance of alpha 1-antitrypsin (alpha 1-AT) as a method of detecting and quantitating intestinal protein loss in patients with inflammatory bowel disease. We investigated alpha 1-AT clearance (C alpha 1-AT) in 14 patients (seven with Crohn's disease, seven with ulcerative colitis) and in 10 children with gastrointestinal disorders and normal serum albumin values who served as controls. The inflammatory bowel disease patients were analyzed for nutritional status, intestinal absorption, disease activity and distribution, and presence or absence of rectal bleeding. alpha 1-AT was measured in stool (72-h collections) and serum by radial immunodiffusion, and the clearance was calculated. The mean C alpha 1-AT in patients with inflammatory bowel disease was significantly (p less than 0.05) higher than that of the controls. C alpha 1-AT in the former patients was inversely related to the serum albumin level (p less than 0.001), but not to disease activity, medications, absorption, nutritional status, or moderate rectal bleeding. In the patients with Crohn's disease there was a trend to increased C alpha 1-AT from only ileal to diffuse small intestinal disease involvement. We conclude that in patients with inflammatory bowel disease, fecal clearance of alpha 1-AT is a useful method for quantitating intestinal protein loss, and that moderate rectal bleeding does not affect the C alpha 1-AT determination.