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Many health benefits are associated with a high dietary intake of vegetables and fruit (VF); however, little effort has been expended to determine whether the botanical families from which high-VF diets are formulated affect their biological activities. The objective of this study was to determine whether the botanical diversity of high-VF diets alters the response in oxidative biomarkers for lipid peroxidation and DNA oxidation. Two diets were developed that varied in botanical diversity and provided 8–10 servings of VF/d. The high botanical diversity diet (HBD) included foods from the 18 botanical families that induced a reduction in oxidative damage of lipids or DNA. The low botanical diversity diet (LBD) emphasized 5 of these botanical families based on reports that their bioactive components had high antioxidant activity. A total of 106 women completed the study. Participants consumed 9.1 6 2.6 and 8.3 6 2.1 servings of VF/d with the LBD and HBD diets. Only the HBD diet induced a significant reduction in DNA oxidation (P, 0.05). Both the LBD and the HBD diets were associated with a reduction in lipid peroxidation (P , 0.01). These findings indicate that botanical diversity plays a role in determining the bioactivity of high-VF diets and that smaller amounts of many phytochemicals may have greater beneficial effects than larger amounts of fewer phytochemicals.