We studied changes in serum cholestanol and plant sterols (indexes of cholesterol absorption) and cholesterol precursors (indexes of cholesterol synthesis) in response to cholesterol reduction by way of 1 year's treatment with atorvastatin (n = 102) and simvastatin (n = 105) treatments in patients with coronary heart disease. Serum cholesterol levels and ratios of the precursor sterols to cholesterol after 1 year of treatment were reduced in proportion to the pretreatment values (33% +/- 1% by simvastatin and 36% +/- 1% by atorvastatin; P <.01 for difference between groups) for cholesterol; the respective reductions in the precursor sterol:cholesterol ratios were also higher with atorvastatin (50% +/- 2% for lathosterol) than with simvastatin (42% +/- 1%; P <.01 between groups), but the ratio of squalene to cholesterol was increased (17% +/- 5%, P <.001) by atorvastatin. Plant sterol concentrations were gradually increased by atorvastatin but decreased initially by simvastatin. However, their ratios with respect to cholesterol were increased by as much as 82% with atorvastatin and by as much as 39% with simvastatin. In conclusion, effective inhibition of cholesterol synthesis and subsequent reduction in serum cholesterol levels by statins lead to increases in serum plant-sterol levels, probably as a result of reduced biliary secretion and enhanced absorption of these sterols. Because serum plant sterols have been claimed to be involved in the early development of atherosclerosis, the question arises whether continuously increasing serum plant sterols during long-term statin treatment should be prevented by cholesterol malabsorption (eg, by plant stanol ester consumption), especially in subjects with high baseline plant sterol values and effective sterol absorption.