The involvement of cytosolic phospholipase A 2 (cPLA 2 ) and ceramide in the accumulation of cholesteryl ester induced by the uptake of oxidized low-density lipoproteins (oxLDL) in macrophages was investigated. Uptake of oxLDL by [ 3 H]oleic acid-labeled macrophages stimulated the formation of cholesteryl oleate, and this process was completely inhibited by a cPLA 2 inhibitor. Under the conditions, a time-dependent increase in ceramide was observed, while sphingomyelin levels were unaffected. The production of ceramide was completely inhibited by fumonisin B 1 , an inhibitor of the de novo synthesis of ceramide, and oxLDL-induced cholesteryl oleate formation was inhibited partially. Treatment of the cells with sphingomyelinase accelerated the formation of cholesteryl ester. Furthermore, sphingomyelinase or cell-permeable ceramide induced the release of oleic acid, and this was inhibited by a cPLA 2 inhibitor. These results suggest that activation of cPLA 2 is responsible for the formation of cholesteryl ester induced by the uptake of oxLDL in macrophages, and that de novo-synthesized ceramide is implicated, at least in part, in this process.