The aim of this study was to assess the effect of the citrus compounds, limonin and nomilin on activities of the phase I cytochrome P450 enzyme system and the phase 11 enzyme glutathione S-transferase (GST) in the liver and small intestine of the rat. Male Wistar rats were fed an American Institute of Nutrition-76 (AIN-76) diet containing increasing doses of limonin or nomilin (1, 2, 5 and 10 mg/day) for 10 days. A control group received the AIN-76 diet alone. The positive control group was fed the control diet containing 3-methylcholanthrene (3-MC; 15mg/day), a known inducer of cytochrome P450 and GST. No significant (P < 0.05) changes were observed in liver and small intestine cytochrome P450 isoenzyme activities from animals fed diets containing limonin or nomilin. In contrast, GST activity increased in a dose-dependent manner in the liver of rats fed diets containing limonin and nomilin. A significant dose-dependent increase in small intestinal GST activity was also observed in nomilin fed animals. Our results add to the increasing body of evidence that these citrus limonoids are inducers of the detoxifying enzyme GST. (C) 2003 Elsevier Inc. All rights reserved.