Studies in cell culture and laboratory animals have shown that green tea and its major component, epigallocatechin-3-gallate, inhibit cell growth and reduce tumor incidence. However, results of epidemiological studies have generated inconsistent, sometimes conflicting data regarding protection by green tea against human cancers. To clarify the findings of these laboratory studies in application to humans, we conducted a pilot intervention study with three heavy smokers (> 10 cigarettes/day) and three nonsmokers (never smokers) in order to evaluate the molecular and cellular effects of drinking green tea using human oral cells as an investigative tool. Green tea total extract (400-500 mg/cup, 5 cups/day) was administered in drinking water to the subjects for four weeks. Two oral cytology samples were taken weekly for measurements of tobacco carcinogen-induced DNA damage, including bulky adducts and oxidized bases, cell growth, DNA content, and apoptosis. The study showed that during the course of green tea administration smoking-induced DNA damage was decreased, cell growth was inhibited, and the percentage of cells in S phase was reduced, cells accumulated in G1 phase (cyclin D1 positive), DNA content became more diploid and less aneuploid, and p53, Caspase-3, and TUNEL, markers of apoptosis, were increased. The study, although preliminary, indicates that drinking green tea reduced the number of damaged cells in smokers by inducing cell growth arrest and apoptosis, a mechanism similar to that observed in cultured cells and animals. These results warrant a large-scale intervention trial to further verify the role of green tea in the prevention of oral cancer in smokers.