Studies employing analysis of LDL subclasses have demonstrated heterogeneity of the LDL response to low fat, high carbohydrate diets in healthy nonobese subjects. In individuals with a genetically influenced atherogenic lipoprotein phenotype, characterized by a predominance of small dense LDL (LDL subclass pattern B), lowering of plasma LDL cholesterol levels by diets with < or =24% fat has been found to represent a reduction in numbers of circulating mid-sized and small LDL particles, and hence an expected lowering of cardiovascular disease risk. In contrast, in the majority of healthy individuals with larger LDL (pattern A, found in approximately 70% of men and a larger percentage of women), a significant proportion of the low fat diet-induced reduction in plasma LDL cholesterol is made by depletion of the cholesterol content of LDL particles. This change in LDL composition is accompanied by a shift from larger to smaller LDL particle diameters. Moreover, with progressive reduction of dietary fat and isocaloric substitution of carbohydrate, an increasing number of subjects with pattern A convert to the pattern B phenotype. Studies in families have indicated that susceptibility to induction of pattern B by low fat diets is under genetic influence. Thus, diet-gene interactions affecting LDL subclass patterns may contribute to substantial interindividual variability in the effects of low fat diets on coronary heart disease risk.