Garlic is reported to have beneficial effects on risk factors associated with cardiovascular disease, including normalization of plasma lipid levels. However, numerous studies do not support this beneficial effect of garlic on plasma lipids. This contradiction may result from the use of different garlic-derived materials, experimental designs, and/or animal models. The present study investigated the hypolipidemic effect of garlic-derived materials in APOE*3-Leiden mice, a model well suited for drug and dietary intervention studies of hyperlipidemia. APOE*3-Leiden mice were fed a garlic-derived sulfur-rich compound, either allicin (0.29 g · L drinking water-1) or diallyldisulfide (0.27 g · kg diet-1), or powdered garlic, of either the kwai (42 g · kg diet-1) or morado (42 g · kg diet-1) variety. The amounts of garlic-derived materials supplied allowed free intake of allicin or allicin equivalents (diallyldisulfide, kwai, or morado) at 44 mg · kg body wt-1 · d-1. Mice were fed a nonpurified diet for 4 wk, followed by a Western diet for 8 wk, both supplemented with the garlic-derived materials. These diets had no consistent effect on plasma lipids and did not affect lipoprotein profiles, which are markers for wholebody cholesterol synthesis and intestinal sterol absorption. The current data indicate that the postulated effects of garlic on cardiovascular disease are not caused via modulation of plasma lipid levels. J. Nutr. 134: 1500-1503, 2004.