The diagnosis of coeliac disease can be confounded in individuals with a self-prescribed gluten-free diet. In this setting, guidelines suggest a gluten challenge for at least 14 days followed by duodenal biopsy, but this recommendation is based on limited evidence. Now, the responses to a 14-day oral gluten challenge (5.7 g per day) have been studied in 19 patients with biopsy-confirmed coeliac disease. The investigators found that mucosal architecture changes were not established in the majority of patients with coeliac disease after 14 days. However, gluten-specific T cell responses in blood, measured by HLA-DQ:gluten tetramers with flow cytometry, were increased twofold by day 6 in 12 of 15 patients evaluated. These findings suggest that the blood-based test is more sensitive and less invasive than biopsy for diagnosing coeliac disease after short-term gluten challenge, and should be further evaluated.