The influence of Ca(2+) and Mg(2+), together with lipoprotein lipase (LPL), on the binding and uptake of Eu(3+)-labeled native and oxidized low density lipoprotein (LDL) to mouse peritoneal macrophages (MPM), and on the deposition of esterified cholesterol in these macrophages, were studied. We found that both LPL and Ca(2+) (but not Mg(2+)) increased the binding and uptake of native and mildly or moderately oxidized LDL, and the subsequent deposition of cholesterol esters in MPM. When added together, LPL and Ca(2+) synergistically increased the binding and uptake of native and oxidized LDL, and the deposition of esterified cholesterol derived from native and mildly or moderately oxidized LDL, in MPM. Since both calcium and LPL are found in the atherosclerotic lesions, our results suggest that Ca(2+) and LPL may synergistically promote foam cell formation and atherogenesis. Furthermore, future research in the metabolism of lipoproteins should take into account the calcium levels in the experimental conditions.