Calorie restriction (CR) prolongs life in animals, but may reduce plasma HDL, important in reverse cholesterol transport (RCT). The effect of CR, 60% of an ad libitum (AL) diet, on cholesterol removal from rectus femoris muscle injected with cationized LDL, was studied in C57BL male mice. RCT in vivo, on CR and AL diet, and cholesterol efflux from macrophages exposed to CR or AL sera, was similar, despite a 22% reduction in plasma HDL-cholesterol (HDL-C). In CR fed mice total cholesterol (TC) and phospholipid (T-PL) decreased by 32% and 38%, while HDL-C and HDL-PL decreased by 22% and 16% only, resulting in increased HDL-PL/T-PL ratio, which enhanced RCT. Partial re-feeding (CR-RF, 70% of AL) induced normalization of plasma lipids (excluding triglycerides), while HDL-PL/T-PL remained elevated. Thus, as CR did not interfere with RCT in vivo, it could possibly be beneficial to patients at risk for coronary heart disease. (C) 2003 Elsevier Inc. All rights reserved.