Apolipoprotein (apo) E and C-I are plasma apolipoproteins that have been implicated in the etiology of atherosclerosis and obesity, respectively. Both proteins are synthesized and secreted by macrophages, though pharmacological regulation of their production is poorly understood. The authors compared the effect of 2 HMG-CoA reductase inhibitors, atorvastatin and cerivastatin, on the synthesis and secretion of apoE and apoC-I by THP-1 macrophages. Atorvastatin reduced medium apoE and cellular apoE mRNA of PMA-activated THP-1 cells in a dose-dependent manner (-24% and -22%, respectively, at 1-μmol/L, P < 0.01). ApoC-I in the medium was also reduced by atorvastatin in a dose-dependent manner, though to a lesser extent (-15% at 1-μmol/L, P < 0.05). Cerivastatin similarly reduced medium apoE (-20% at 1-μmol/L, P < 0.05) and cellular apoE mRNA (-31% at 1-μmol/L, P < 0.05), and significantly lowered cellular apoC-I mRNA (-15%, P < 0.05), but not apoC-I in the medium. 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