Microautoradiographic measurements of TdR3H incorporation into epithelial cells of colonic biopsies were compared in normal and eight index cases with familial polyposis, an inherited trait characterized by the development of colonic polyps and carcinomas. Colonic epithelial cells normally synthesized DNA synthesis was proliferated in the deeper two-thirds of the crypts, while DNA synthesis was repressed in the upper one-third. Patients with familial polyposis and patients with isolated single polyps incorporated TdR into epithelial cells lining the surfaces of polyps and occasionally into surface cells of intervening flat mucosa. Symptom-free members of polyposis families also demonstrated TdR3H incorporation into surface epithelial cells in biopsies of morphologically flat mucosa. The findings indicate similar proliferative behavior of epithelial cells in the formation of all adenomas, be they single isolated polyps or multiple familial adenomatous polyps. A sequence of changes occurs involving a loss of the cells' ability to repress DNA synthesis and the appearance of cells with persistent DNA synthesis at the surface and along the upper portion of colonic crypts. These defects are focal and widespread in the colonic mucosa of those with familial polyposis and are expressed at early age.