We examined the relationships of I405V cholesteryl ester transfer protein (CETP), Taq1B CETP and apolipoprotein (apo)E polymorphisms with the pattern of response to dietary plant sterol ester (PSE) by plasma lipids and CETP concentrations as well as lecithin-cholesterol acyltransferase (LCAT) activity. Subjects with moderate primary hypercholesterolemia (20-60 y old; 50 women; 10 men) consumed margarine (20 g/d) without (placebo) or with PSE (2.8 g/d = 1.68 g/d phytosterols) for 4 wk each period, in a crossover, double-blind study. Plasma CETP concentration was measured by ELISA; endogenous LCAT activity was expressed as the percentage of esterification (30 min incubation) of the subjects' (14)C-unesterified cholesterol HDL. PSE reduced concentrations of plasma total cholesterol (TC) (10%) and LDL cholesterol (LDL-C) (12%). In relation to the I405V CETP polymorphism, the percentage reductions in TC with consumption of PSE for the II, IV and VV phenotypes were 7.2, 4.2 and not significant, respectively, whereas LDL-C significant reductions occurred only for II (9.5%). However, the CETP concentration diminished only in the II phenotype.