The ability of HDL to promote the efflux of cholesterol from macrophage foam cells is thought to be central to its antiatherogenic properties. The active transport of cholesterol from macrophage foam cells to plasma HDL or apoA-1 is mediated by ABCG1 or ABCA1, respectively. In most reports, transplantation of ABCG1−/− bone marrow in atherosclerosis-susceptible recipient mice results in unchanged or reduced atherosclerosis, reflecting compensatory upregulation of ABCA1 or increased apoptosis of ABCG1 deficient macrophages. Transplantation of ABCA1−/−ABCG1−/− bone marrow in LDL receptor deficient mice results in dramatic leukocytosis, infiltration of multiple organs with foam cells, and neutrophils and accelerated atherosclerosis. ABCG1 is also highly expressed in endothelial cells and has a major role in efflux of cholesterol and 7-oxysterols. ABCG1−/− mice display markedly impaired endothelium-dependent relaxation, reflecting reduced formation of the active, dimeric form of eNOS. The combined activities of ABCA1 and ABCG1 have important antiatherogenic and anti-inflammatory roles, acting in both macrophage foam cells and endothelium.