Transgenic alfalfa (Medicago sativa L.), which accumulated resveratrol-glucoside (RG), was incorporated into diets and fed to female, 6-wk-old CF-1 mice for 5 wk. Mice fed diets containing transgenic alfalfa with supplemented alpha -galactosidase had significantly fewer azoxymethane (AOM)-induced aberrant crypt foci (ACF) in their colon relative to mice fed the transgenic alfalfa diets without added alpha -galactosidase (P = 0.02). Resveratrol-aglycone (Rag) was detected in the colon of 100% of mice fed transgenic alfalfa diets with supplemented alpha -galactosidase and in 60% of mice fed transgenic alfalfa without alpha -galactosidase (P < 0.05). Colonic concentrations of Rag (< 0.5 nmol/g tissue) in mice fed transgenic alfalfa with alpha -galactosidase (0.22 +/- 0.18 nmol/g tissue) tended to be higher than in animals fed diets without alpha -galactosidase (0.1 +/- 0.08 nmol/g tissue; P = 0.09). The use of N-(Bn-butyl)-deoxygalactonojirimycin, an inhibitor of lactase-phlorizin hydrolase (LPH), in transport studies with everted jejunal sacs from CF-1 mice (N = 8) suggested that LPH is involved in the intestinal deglycosylation of RG. Our collective findings suggest that RG from transgenic alfalfa is metabolized and absorbed in the upper intestine and does not reach the colon in sufficient amounts to inhibit ACF.