Technical Abstract: Acute lymphoblastic leukemia (ALL) with translocation t(4;11) is a high-risk leukemia found in 60-85% of infants with ALL and is often refractory to conventional chemotherapeutics after relapse. Although resveratrol is able to kill high-risk leukemia in vitro, this agent has not been evaluated against this disease in vivo. The efficacy of dietary resveratrol as a preventative agent against this leukemia was evaluated in NOD.CB17-Prkdcscid/J mice engrafted with the human t(4;11) ALL line SEM. Five wk old mice were placed on control diet or a diet containing 0.2% w/w resveratrol. After 3 wk on the diets, SEM cells were injected into the tail veins of all mice, and engraftment was monitored by evaluating the presence of human CD19+ cells in peripheral blood using flow cytometry. Dietary resveratrol did not delay engraftment of the leukemia cells. To determine if resveratrol could increase efficacy of a chemotherapeutic agent, vincristine was injected intraperitoneally into leukemic mice maintained on the different diets. Survival curves and monitoring the percent of human leukemia cells in peripheral blood showed that leukemia cell growth was not inhibited by dietary resveratrol and this dietary nutrient did not potentiate the activity of vincristine. These data suggest that dietary resveratrol does not have potential as a novel preventative agent against the growth of high risk t(4;11) ALL in vivo.