In view of the importance to the patient of demonstrating mucosal sensitivity to gluten we have quantitated morphologic change during organ culture of small bowel mucosa by measuring enterocyte height. In 27 normal controls the mean preculture enterocyte height was 28.3 micrometer +/- 1.8 (+/- 1 SD), decreasing to 25.6 micrometer +/- 1.9 and 26.1 micrometer +/- 2.0 after 24 h culture in the absence and presence of gluten, respectively. Both these decreases were significant (p < 0.001), but there was no difference between culture with or without gluten. In 9 abnormal controls, the mean preculture enterocyte height was 27.0 micrometer +/- 2.7, decreasing significantly (p < 0.05) to 24.5 micrometer +/- 1.1 after 24 h culture without gluten, and to 25.4 micrometer +/- 2.3 with gluten (NS). In 17 untreated celiac patients, the mean preculture enterocyte height was 19.6 micrometer +/- 1.9 increasing significantly to 23.8 micrometer +/- 2.0 (p < 0.001) after 24 h culture without gluten but decreasing to 18.7 micrometer +/- 3.1 after 24 h culture with gluten (NS). There was a significant difference between culture with or without gluten (p < 0.001). In 21 treated celiac patients, the mean preculture enterocyte height was 28.1 micrometer +/- 1.9 decreasing to 25.4 micrometer +/- 2.0 and 24.2 +/- 1.9 in the absence and presence of gluten, respectively. Both these decreases were significant (p < 0.001), but more importantly there was a significant decrease (p < 0.001) after culture with gluten compared with culture without gluten. These data indicate that it is possible to quantify morphologic change during organ culture and to demonstrate gluten-sensitivity not only in untreated, but also in treated celiac mucosa. These studies have important implications as regards the diagnosis and further investigation of the etiology of celiac disease.