In ad lib.-fed rats the epithelium of the small intestine, like the liver, contains large quantities of glutathione, 17.0 and 32.4 nmol/mg protein respectively. Following 24 h food restriction the glutathione content in both tissues fell 53 and 69% respectively. Unlike the liver, however, the glutathione content of the intestinal mucosa is not regulated to a diurnal rhythm, suggesting that the liver may provide glutathione or glutathione precursors to maintain intestinal glutathione levels. Intestinal epithelial cell preparations obtained from 24 h food-deprived rats had depleted glutathione stores (50%) and as a consequence were more susceptible to the oxidizing effects of cumene hydroperoxide. These results suggest that if glutathione plays a major role in the defence of the intestinal mucosa from ingested toxins then depletion of this defence during periods of food restriction could significantly increase the susceptibility of the individual to toxins present in the diet.