Epidemiologic studies have shown that hypercholesterolemia is associated with increased left ventricular (LV) mass. Free radicals have been shown to be increased in hyperlipidemic patients. This study sought to determine whether pravastatin administration can affect LV mass in patients with untreated total cholesterol ≥240 mg/dl by reducing 8-iso-prostaglandin F2α concentrations, a reliable marker of oxidant injury. Fifty patients were randomly assigned to one of two groups, one with (n = 25) and one without (n = 25) treatment with pravastatin (10 or 20 mg/d). A group of normolipidemic control subjects was used for comparison. Echocardiograms were performed at baseline and after 6 months of therapy. Hyperlipidemic patients showed significant increases in LV mass index at baseline compared with the normolipidemic control group (125 ± 8 vs. 107 ± 5 g/m, p < 0.0001). Pravastatin treatment significantly reduced plasma total and low-density lipoprotein cholesterol levels, as well as increased high-density lipoprotein cholesterol. After 6 months of therapy with pravastatin, the magnitude of LV mass regression correlated with the magnitude of inhibition of free radical formation assessed by 8-iso-prostaglandin F2α formation (r = 0.67, p = 0.002). Multivariate analysis revealed that regression of LV mass was significantly correlated only with the changes in 8-iso-prostaglandin F2α (p < 0.0001, adjusted R = 0.83). These findings demonstrated for the first time that in addition to its primary anti-lipidemia, pravastatin may have an additional effect of reducing LV mass–independent lipid-lowering effects, possibly through attenuation of free radical formation.