The proliferative characteristics of epithelial cells in rectal biopsies from a group of 18 patients (ages 18–72) with ulcerative colitis spanning several months to over 20 years duration were examined, using anin vitro3HTdR labeling technique. Although the labeling indices for patients with inflammatory bowel disease did not differ significantly from that of control (8.9<±3.6 vs 7.7±3.9), the number of labeled cells I individual crypt column was higher among some crypts in ulcerative colitis patients. A normal proliferative pattern was demonstrated in crypts of 5/18 patients (27.8%) with DNA synthesis confined to the lower two-thirds of the crypt and the lower third the major zone of proliferation. Thirteen patients (72.2%) showed extension of the proliferative compartment to the surface of the glands, while retaining the lower third of the gland as the predominant proliferative zone (Stage I abnormality). Of these 13, seven had an additional abnormality, namely, a shift of the major zone of proliferation to the middle third of the crypt (Stage II abnormality), a pattern first reported in the colorectal mucosa of patients with a history of colon cancer. Precancerous lesions, including incompletely differentiated epithelium and lateral crypt budding, were recognized in all of these cases, suggesting that the Stage II abnormality is a proliferative parameter forecasting neoplastic transformation.