Current dietary recommendations advocate reductions in saturated fatty acids (SFA) and cholesterol (C) as a primary intervention for achieving a more desirable plasma lipid profile. To ascertain whether it is more efficacious to decrease dietary lauric and myristic acids (12:0 + 14:0) or dietary palmitic acid (16:0) in conjunction with a reduction in dietary C, 11 rhesus monkeys (8 males, 3 females) were initially fed a control diet rich in SFA + C for 14 wk [dietary fat approximately 38% of energy (%en), SFA 16%en and C at 180 mg/1000 kcal]. Plasma lipids were measured between the 9th and 13th wk, and LDL metabolism was assessed after 13 wk. Monkeys were then split into two groups and fed one of two American Heart Association (AHA) Step 1 diets (approximately 30%en fat, 10%en SFA, 75 mg cholesterol/1000 kcal) for an additional 14 wk, and plasma lipids and LDL metabolism were re-evaluated. Group 1 received a 16:0-rich diet in which most 12:0 + 14:0 were deleted (approximately 8.6%en from 16:0 and approximately 0.3%en from 12:0 + 14:0), whereas Group 2 received a diet rich in 12:0 + 14:0 from which 16:0 was selectively removed (2.6%en from 16:0 and approximately 6.3%en 12:0 + 14:0). In all three diets, oleic and linoleic acid were held relatively constant so that only SFA, the level of total fat and cholesterol were manipulated. Only the Step 1 diet that selectively removed 12:0 + 14:0 (the 16:0-rich diet) significantly reduced all lipid fractions, including total cholesterol (TC), HDL-C, LDL-C, apolipoprotein B (apoB) and the LDL pool size. Plasma triglyceride (TG) and the ratio of TC/HDL-C were not altered by either Step 1 diet. The smaller LDL pool size following the 16:0-rich diet in Group 1 was attributable to a significantly higher fractional catabolic rate (FCR) of LDL because the transport rate of LDL apoB was unaffected. Although the FCR was increased with the 12:0 + 14:0-rich diet, the LDL apoB pool was not affected because the transport rate of LDL tended to increase as well. The data suggest that a Step 1 diet that reduces total fat by decreasing 12:0 + 14:0 in conjunction with dietary C, improves plasma lipids more favorably than a similar diet that selectively removes 16:0 and C. Previous data would imply that the benefit resulted from removal of 12:0 + 14:0 per se, but the possibility is not eliminated that removal of C (independent of 12:0 + 14:0) muted the potential interaction between C and palmitic acid that tends to raise TC.