Twenty colonoscopies (eight complete or almost complete; 12 short) were carried out on 15 patients with ulcerative colitis with the aim of comparing the endoscopic aspects with the light and electron microscopic features in biopsies taken from multiple sites. Patients with severe attacks were examined without prior preparation (two examinations). When the attack was mild to moderate (11 examinations), or the patient was in remission (seven examinations), two saline enemas were given up to 1 h before examination. There was a favorable correlation between the endoscopic and light microscopic features in 94.7% of the biopsies (total number of biopsies, 76). The electron microscope findings greatly exceeded those observed by light microscope and indicated that the major abnormality resides within the colonic epithelial cells. Distinctive ultrastructural changes were present both in apparently uninvolved (endoscopically and histologically) parts of colon and in inactive stages of ulcerative colitis. These findings suggest that colonic mucosal involvement may be universal, persist during clinical remission, and precede the light microscopic findings. They also support the importance of maintenance therapy.