We considered the role of scanning electron microscopy (SEM) in clinical investigation of different gastrointestinal diseases. The following clinical applications of SEM may be suggested on the basis of our original data and those reported in literature: in peptic ulcer: assessment of the completeness of healing, by observing the mucosal surface architecture of the scars; identification of mucosal changes, namely enterocytic surface membrane alterations, predictive of recurrence; in coeliac disease: early assessment of the response to gluten-free diet and follow-up of the patients by staging the process of mucosal repair in cerebriform, intermediate and villous patterns; in ulcerative and Crohn's colitis: enhancement of the diagnostic sensitivity of perendoscopic biopsy, by detecting differences in surface structure of mucosa surrounding ulcers in both diseases. This is subverted in ulcerative colitis and preserved in Crohn's colitis. Finally the complementary role of SEM in relation to endoscopy and light microscopy is emphasized.