This proposal is a prospective investigation of the role of periodic clinical, roentgenologic, sigmoidoscopic and colonoscopic biopsy and cytologic collections, and plasma and colonic CEA as to their predictive value in the detection of colonic carcinoma and ulcerative colitis. It employs a skilled team consisting of gastrointestinal clinicians, a pathologist, a radiologist, gastrointestinal morphologist, a gastroenterologist skilled in radio-immune assay, and a cytologist. New features of this proposal include 1) the addition of colonoscopic observations, biopsy collection, and cytology collection 2) electron microscopic studies to more accurately define stages of differentiation of precancer 3) correlation of serial serum and colonic CEA determinations with the above observations 4) organ culture and electron microscopic studies to further search for etiologic clues in ulcerative colitis. This study is designed to control observations as much as possible while attempting to answer the question as to when prophylactic total colectomy in patients with ulcerative colitis should be recommended in order to prevent carcinoma of the colon without premature recommendation of total colectomy. The electron microscopic studies will further permit us to define, at the ultrastructural level, the stages of differentiation of mucosal biopsies in patients with prolonged ulcerative colitis and permit us to compare it to our own and previously reported studies at the light microscopic level.