1. The combination of a wire-mesh support with the roller-tube technique is described as a procedure for the culture of human jejunal mucosa in vitro. 2. The technique has been applied to fragments (approximately 10 mg) of jejunal biopsies from both normal subjects and patients with coeliac disease. 3. The cultured tissue has been shown by radioautography to incorporate [ 3 H]leucine into proteins of the villus epithelial cells and [ 3 H]thymidine into nucleic acid, predominantly by the enterobiasis. 4. Although the tissue protein and DNA contents fall during culture, it was found that the combined tissue and medium DNA content remained constant during culture and may be used as a reference for enzyme and biochemical studies on cultured intestinal biopsies.

1. Reduced activities of four enzymes from brush borders were found in intestinal biopsies from patients with untreated coeliac disease. The activities returned towards control values after treatment by gluten withdrawal. Parallel changes were noted for the cytosol enzyme lactate dehydrogenase. 2. Measurement of brush-border integrity by differential centrifugation of biopsy extracts indicated increased fragility of the brush borders in biopsies from untreated patients. Normal values were obtained for biopsies from treated patients. 3. Increased activities of six acid hydrolases (lysosomal enzymes) were found in biopsies from untreated coeliac patients. Normal values were obtained for biopsies from treated patients. 4. Assessment of lysosomal integrity by assay of latent N -acetyl-β-glucosaminidase and of sedimentable activity of four acid hydrolases demonstrated increased lysosomal fragility in untreated coeliac mucosa. These lysosomal changes return to within the normal range after treatment by gluten withdrawal. 5. The lysosomal changes are consistent with their having a pathogenic role in the enterocyte damage of coeliac disease. Possible mechanisms for the lysosomal changes are discussed.