A diet rich in fruit and vegetables is associated with decreased risk of disease. One possible mechanism for this is that dietary antioxidants positively regulate protective genes. Toward our goal to identify bioactive compounds with such functions in plants, we developed transgenic mice that express luciferase controlled by the gamma-glutamylcysteine synthetase heavy subunit (GCS(h)) promoter. Mice that consumed a nonpurified diet ad libitum were supplemented with juices or extracts of antioxidant-rich berries for 42 h or 3-4 wk. The treatments generally increased luciferase activity in brain and skeletal muscle and decreased it in liver compared with controls fed water. The same overall pattern was also found in mice fed ellagic acid (EA), a phenolic acid found in many berries. This change in GCS(h) promoter activity after berry treatment occurred in only approximately 50% of the mice, indicating that they were either responders or nonresponders. Our results demonstrate for the first time that berry extracts rich in polyphenols and EA can induce GCS(h) in vivo. The induction of protective enzymes may be important for the chemopreventive effects of fruits and vegetables.