After a long-term culture in (-)-epigallocatechin gallate (EGCG, 20 microM), a major constituent of green tea, human gastric AGS cells developed 2.2-fold resistance to EGCG. The resistant AGS (AGS-R) cells were cross-resistant to several N-methylcarbamate insecticides, which are among the major control agents for pest insects in Taiwan. The AGS-R cells also showed protective effects against both the cytotoxicity and DNA damage induced by one of the mutagenic derivatives of N-methylcarbamate insecticide, N-nitroso methomyl, which is known to target the mammalian gastric tract. Therefore, acquisition of resistance by AGS cells through chronic exposure to EGCG implies that the tea-drinking habit of the Taiwanese is probably beneficial for the health of the gastric tract. In addition, AGS-R cells were cross-resistant to sodium arsenite and hydrogen peroxide, indicating that tolerance to oxidative stress might play a role in the development of resistance described in this investigation.