This report summarizes two studies which investigated the effects of apolipoprotein E (apoE) polymorphism on the serum total cholesterol (TC) and lipoprotein cholesterol responses to 8:0 + 10:0 and 12:0 diets (Study I) and 14:0, 16:0 and 18:0 diets (Study II). Eighteen healthy premenopausal women (3 apoE 3/2, 12 apoE 3/3, 3 apoE 4/3) in study I and another 18 healthy premenopausal women (4 apoE 3/2, 10 apoE 3/3, 3 apoE 4/3, 1 apoE 4/2) in study II consumed a baseline diet providing 40 en% total fat, 11 en% 18:2, 15 en% 18:1, 11.5 en% saturated fat for the first week of each 5-wk period. The experimental diets for both studies provided 40 en% total fat, 13-14 en% as one of five test saturated fatty acids (SFA), 14-16 en% 18:1, and 3-4 en% 18:2. Analysis by apoE phenotypes showed that both the 8:0 + 10:0 diet and the 12:0 diet in Study I induced significant increases in serum TC in subjects with different apoE phenotypes with the exception of apoE 3/2 in the medium-chain triglyceride group. In contrast, in Study II, individuals with apoE 4/3 consuming the 14:0 diet showed significant increases in serum TC, high density lipoprotein-cholesterol (HDL-C), and HDL2-C, but the same subjects consuming the 16:0 diet showed significant increases in serum TC and low density lipoprotein-cholesterol. The findings from both studies indicated serum lipoprotein responses to SFA were different and the variation of responsiveness may be regulated, at least in part, by apoE polymorphism, especially when 14:0, 16:0, or 18:0 was consumed.