Induction of apoptosis has been suggested as a mechanism for the anti-carcinogenic effect of tea constituents in animals and in vitro studies. We addressed this hypothesis in a human study. Study participants were consecutive patients who underwent colonoscopy at the UNC Hospitals (August 1998 to March 2000). Biopsies were taken from normal rectal mucosa. Apoptosis was scored by the terminal deoxyribonucleotide transferase-mediated digoxigenin dUTP nick end labeling (TUNEL) method and by standard morphological criteria. The analysis included 171 patients with adenomas (cases) and 323 adenoma-free controls. After adjusting for sex, age, race, and BMI, apoptotic score was inversely associated with adenoma: the odds ratios (ORs) for linear trend associated with tertiles were 0.3 (0.3-0.5) for morphologic score and 0.5 (0.4-0.6) for the TUNEL score, respectively. Tea consumption (2-3 and >3 versus <2 servings/day) showed a weak negative association with adenoma: the ORs were 0.7 (0.3-1.4) and 0.5 (0.2-1.1), respectively. Neither measurement of apoptotic score changed by the level of tea consumption (P value for Kruskal-Wallis test > or =0.5). We did not find statistical interaction between apoptotic score and tea consumption. Tea exposure is not associated with apoptosis in normal rectal tissue in vivo.