Our aim in this study was to monitor changes of the intestinal structure by alpha 1-antitrypsin clearance (alpha 1-ATCL) in order to offer an alternative to the gluten challenge biopsy. In addition, we evaluated the possibility of reducing the time of gluten challenge. Twelve patients had a presumptive diagnosis of celiac disease based on clinical and histological grounds. They were studied when the jejunal histology was normal after gluten-free diet and an alpha 1-ATCL was normal. The gluten was introduced by returning to a normal diet. The challenge lasted 4 wk. We measured alpha 1-ATCL at the end of the 1st and 4th wk, and a new jejunal biopsy was obtained at the end of the 4th wk. By wk 1, alpha 1-ATCL was abnormal in 11 patients but normal in one. By wk 4, alpha 1-ATCL was abnormal in 10 patients and still normal in one. The post-challenge biopsies showed atrophy in 11 and was normal only in the patient with normal alpha 1-ATCL at wk 1 and 4. One patient with abnormal alpha 1-ATCL had to stop the challenge at the first week. The patient with normal clearance at wk 1 and 4 and normal biopsy at wk 4 had abnormal results at 6 months. These data support our hypothesis that alpha 1-ATCL can be used as evidence of gluten toxicity after gluten challenge, and that this test can be abnormal as early as 1 wk after gluten is reintroduced.