Alpha-1-antitrypsin is a glycoprotein which is excreted in feces under three different forms of molecular weight 38, 45 and 51 kDa. The 45 and 38 kDa forms are the result of a partial or total removal of the carbohydrate moiety, respectively. We determined the molecular forms of fecal alpha-1-antitrypsin in 10 controls, 13 patients with protein-losing enteropathy other than inflammatory bowel disease, 70 patients with active (n = 55) (CDAI greater than 150) and inactive (n = 15) (CDAI less than 150) Crohn's disease, 14 patients with active (n = 12) and inactive (n = 2) ulcerative colitis, and 17 patients with ileostomy. Fecal 38 kDa alpha-1-antitrypsin was found in all controls, all patients with protein-losing enteropathy, in 82 percent of patients with inactive inflammatory bowel disease, and in 20 percent of patients with active inflammatory bowel disease. In contrast, the 51 kDa and 45 kDa forms were present in feces of 80 percent of patients with active inflammatory bowel disease, and in only 17 percent of patients with inactive inflammatory bowel disease. Patients with Crohn's disease and the 51 kDa form (n = 39) had significantly higher values of activity index (CDAI) and orosomucoid than patients with Crohn's disease and the 38 kDa form (n = 26) (P less than 0.01). Deglycosylated 38 kDa alpha-1-antitrypsin was never recovered in ileostomy samples. This suggests that deglycosylation of alpha-1-antitrypsin occurred in the colon and is impaired in patients with active inflammatory bowel disease.