Using an in vitro double labeling technique with two different levels of 3H-thymidine, the duration of the phase of DNA synthesis (S) and the labeling index (LI) were measured in the colorectal mucosa of three groups of patients: patients with colorectal neoplasms (adenomas and/or adenocarcinomas), patients with inflammatory bowel disease, and a control group of patients without gastrointestinal pathology. In those patients with colorectal neoplasms, samples were obtained from both the neoplastic mucosa and from the normal appearing mucosa at various distances from the lesions. One-way analyses of variance were used to test the equality of mean S-phase duration and LI in the various types of tissues. S-phase duration was significantly longer in the tumor than in the unaffected mucosa of patients with adenocarcinoma (18.65 hours +/- 2.3 versus 10.13 hours +/- 1.26 P less than 0.0001). However, S-phase duration was significantly longer in the unaffected mucosa of cancer patients than in the mucosa of patients without gastrointestinal pathology (10.58 hours +/- 1.84 versus 7.91 hours +/- 0.46, P = 0.013). Similarly, LI was significantly higher in the unaffected mucosa of patients with adenoma and adenocarcinoma than in the mucosa of patients without gastrointestinal pathology (19.1% +/- 3.0 versus 9.5% +/- 2.2, P less than 0.0001). There was a highly significant trend to a progressive increase of LI from flat histologically normal appearing mucosas to inflammatory mucosas, adenomas, and adenocarcinomas (P less than 0.0001). These results suggest that increased S-phase duration is specifically related to cancer. In mucosa without histologic sign of malignancy, an increased S-phase duration would indicate that the malignant process has started. An increased LI would appear to relate to the selective advantage that rapidly proliferating cells hold over less proliferating ones.