Lyst beige (beige) mice crossed with LDL receptordeficient (LDLr ؊ / ؊ ) mice had a distinct atherosclerotic lesion morphology that was not observed in LDLr ؊ / ؊ mice. This morphology is often associated with a stable plaque phenotype. We hypothesized that macrophage expression of the beige mutation accounted for this distinct morphology. Cultured bone marrow-derived macrophages from LDLr ؊ / ؊ and beige,LDLr ؊ / ؊ mice were compared for their ability to accumulate cholesterol, efflux cholesterol, migrate in response to chemotactic stimuli through Matrigel ® -coated membranes, and express matrix metalloproteinase 9 (MMP9). No differences in cholesterol metabolism were identified. Beige,LDLr ؊ / ؊ macrophage invasion in vitro appeared to be less than LDLr ؊ / ؊ macrophage invasion but did not achieve significance. Nevertheless, tumor necrosis factor-␣ -induced MMP9 expression, secretion, and enzymatic activity of beige,LDLr ؊ / ؊ macrophages were all significantly decreased compared with those of LDLr ؊ / ؊ macrophages ( P Ͻ 0.05).