Elevated plasma levels of remnant lipoproteins and small, dense low-density lipoprotein (LDL) particles increase the risk of atherosclerosis. This prospective, placebo-controlled, crossover trial evaluated the effect of atorvastatin on various lipid parameters including remnant lipoproteins and small, dense-LDL cholesterol levels. Forty-five subjects were enrolled in the study. These subjects fell into three distinct lipid patterns: atherogenic dyslipidemia, isolated hypercholesterolemia, and mixed dyslipidemia. Regardless of the baseline lipid profile, atorvastatin (10 mg q x d) reduced levels of remnant lipoproteins by 25%, LDL-cholesterol by 27%, and the three LDL subfractions by 23%-28% (p<0.0001 for all). Combining all patients, atorvastatin did not significantly alter the overall LDL subfraction pattern; however, in the isolated hypercholesterolemia group, the proportion of LDL present as the small, dense fraction increased by 23% (p=0.01) with treatment, whereas it did not change significantly in the other two groups. Overall, atorvastatin reduced triglycerides by 18% and apolipoprotein-B100 by 23% and increased high-density lipoproteins by 6.2% (p<0.001 all). Since atorvastatin is known to reduce the risk for coronary heart disease events and these data suggest that it does not appear to alter the LDL subfraction pattern, it is unclear whether or not the latter is an important risk predictor independent of LDL-cholesterol concentrations. Increased attention should be paid to absolute concentrations of LDL subfraction cholesterol, which may be a more sensitive indicator of coronary heart disease risk than total LDL or an LDL pattern.