High concentration of fluorine is noxious to the health of humans and animals. Analysis of fluoride in water samples meant for human consumption in the Vellore District of Tamil Nadu, India, revealed its presence above the permissible limit (4.56 ppm). The present study was aimed to investigate the toxic effects of oral administration of the water sample that contains the highest fluoride content on the status of pathophysiological parameters and lipid peroxidation in experimental rats. A positive control group orally treated with 4.5 ppm of fluoride was also included in the study. The assay of pathophysiological enzymes and histological observations made on the stomach and intestinal tissue have revealed the toxic effects of fluoride intoxication. The observed increase in the levels of thiobarbituric acid reactive substances (TBARS) both in plasma and in intestinal epithelium, with a concomitant decrease in both enzymatic and nonenzymatic antioxidants in the plasma of experimental rats, revealed that the altered antioxidant status during fluoride intoxication may be due to increased free radical generation. Copyright 2007 Prous Science.