The change over time in the extent of colonic involvement in ulcerative colitis has, to date, been assessed only by radiological means. To study this issue further, we examined, with repeated colonoscopies, 31 patients with ulcerative colitis. Serial biopsies were taken every 5 cm from the most proximal area reached by the colonoscope down to rectum. The endoscopic and histological extents were evaluated, and the severity of the inflammatory process was graded. Clinical scoring also was performed at the time of both colonoscopies. A change of extent was found in 77% of the patients endoscopically, and in 58% histologically, during a mean follow-up period of 17 months. Extension and regression were demonstrated in the same number of patients. In 61% of 62 procedures, there was complete agreement between colonoscopic and histological extents. The histological extent exceeded the colonoscopic extent in 28% of the procedures. We have the impression that change in the disease extent is a frequent event, and may be a part of the natural history of ulcerative colitis, rather than the exception.