We evaluated fecal clearance of α1-antitrypsin (α1-AT) as a method of detecting and quantitating intestinal protein loss in patients with inflammatory bowel disease. We investigated α1-AT clearance (Cα1-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. α1-AT was measured in stool (72-h collections) and serum by radial immunodiffusion, and the clearance was calculated. The mean Cα1-ATin patients with inflammatory bowel disease was significantly (p < 0.05) higher than that of the controls. Cα1-ATin the former patients was inversely related to the serum albumin level (p < 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 Cα1-ATfrom only ileal to diffuse small intestinal disease involvement. We conclude that in patients with inflammatory bowel disease, fecal clearance of α1-AT is a useful method for quantitating intestinal protein loss, and that moderate rectal bleeding does not affect the Cα1-ATdetermination.