The effects of National Cholesterol Education Program (NCEP) Step 2 diets on plasma lipoprotein profiles in 72 men [mean (+/- SD) age: 44 +/- 15 y, range: 19-81 y] and 48 women (mean age: 50 +/- 21 y, range: 21-78 y) participating in five previously published studies were examined. Subjects were placed on a baseline diet similar to an average American diet (35-41% total fat, 13-16% saturated fat, 31-45 mg cholesterol/MJ) and then on an NCEP Step 2 diet (18-29% total fat, 4-7% saturated fat, 11-20 mg cholesterol/MJ) under isoenergetic conditions. All food and drink were provided. Compared with the baseline diet, consumption of the NCEP Step 2 diets was associated with significant decreases in concentrations of low-density-lipoprotein (LDL) cholesterol (-18.9% and -15.6%, respectively) and high-density-lipoprotein (HDL) cholesterol (-17.0% and -11.2%, respectively) in both men and women. Men with the apolipoprotein (apo) E 3,4 phenotype had a significantly greater decrease in LDL cholesterol (-24.2%) with the NCEP Step 2 diets than men with the apo E 3,3 phenotype (-17.7%). Men with the apo A-IV 1,2 phenotype tended to have less LDL cholesterol lowering (-12.8%) than men with the apo A-IV 1,1 phenotype (-19.6%), but this difference was not significant. No differences were seen by apo E and A-IV phenotype in women. A large variability in lipid response to the diet was observed, with changes in LDL cholesterol ranging from +3% to -55% in men and and from +13% to -39% in women. Forty-eight percent of the variability in LDL-cholesterol response (in mmol/L) to the diet could be accounted for by baseline LDL concentrations and age in men, and 13% by age in women.