At endoscopy, the duodenum in Whipple's disease frequently appears abnormal and some clinical features such as gastrointestinal blood loss and anaemia suggest epithelial damage. However, the intestinal epithelial cells themselves appear to be normal on light and electron microscopy. The aims of this study were to analyse in detail the cytological changes in epithelial cells over time and in response to therapy in biopsies obtained from 20 patients, to investigate the functional repercussion on digestive enzymes such as lactase, and to assess the expression by the epithelial cells of MHC antigens. Cytological changes were minimal at both the light- and the electron-microscopic level and MHC class I expression was preserved. However, changes indicative of functional deficits were demonstrated. Lactase and MHC class II expression were reduced or even absent. Antibiotic therapy resulted in normalization within 3-6 months. These findings are consistent with the clinical evolution and are of interest with regard to the importance of the immune response in aetiopathogenesis.