An abnormal zone of DNA synthesis at the surface and upper portion of colonic crypts has been thought to be related to future adenomatous polyp development and to express a regulatory defect in the mechanism that normally terminates synthesis in the upper third. As part of a screening program for early colon cancer detection, patients over 40 years of age found to have occult blood in their stool (Ho+) are evaluated by barium enema and colonscopy as well as isotopic incorporation studies of biopsy and lavage specimens. This proliferative abnormality occurred most frequently among patients with an adenoma or adenocarcinoma although the frequency varied among simultaneous biopsies from the same patient. Specimens from Ho+ patients with a tumor often contained small areas of focal atypism in the biopsy or fragments of atypical epithelial cells in the lavage sample. A small group of Ho+ patients in whom no overt neoplasm could be detected also demonstrated surface-labeled epithelial cells with morphological alteration of these cells. Based on the microscopic findings presented, continued surveillance of these patients is suggested, as well as extension of these studies to include other high risk groups.