Heart attacks frequently occur in normolipidemic subjects with low concentration of high density lipoproteins (less than or equal to 35 mg/dL). A low-fat diet is generally recommended to patients with coronary heart disease. A low-fat diet decreases both lo tv density (LDL) and high density lipoproteins (HDL), We have shown that on an Average American Diet, subjects with different HDL-cholesterol (HDLC) levels have different HDL subpopulation profiles. in low HDL-C subjects (less than or equal to 35 mg/dL), the apoA-I-only subpopulation oil is significantly decreased compared to individuals with normal HDL-C levels (>35 mg/dL). We hypothesized that as subjects with low HDLC already have low HDL concentrations, the major decrease of HDL-C will occur in subjects with normal HDL-C when a low-fat diet is consumed. Normolipidemic male subjects consumed three diets differing in total fat and saturated fat composition (AAD: 37%, Step-1: 28%, Step-2: 24% total fat) for 6 weeks in a three-period double-blind randomized crossover design, Plasma lipids and apolipoproteins were determined and changes in distribution of HDL subpopulations were evaluated. As a result of a low-fat diet, low HDL-C individuals slightly decreased their HDL-C, but substantially decreased their LDL-C resulting in a significant improvement in the LDL-C/HDL-C ratio. However, subjects with normal HDL-C levels decreased both their LDL-C and HDL-C resulting in an unchanged LDL-C/HDL-C ratio, We also observed significant differences in response to low-fat diets in HDLC and alpha(1) concentrations between low and normal HDLC subjects. In the normal HDLC group, consumption of a low-fat diet also resulted in redistribution of apoA-I-containing HDL subpopulations, indicated by a decrease in the large apoA-I-only alpha(1) subpopulation. These data demonstrate that male subjects with low HDL-C respond to a low-fat diet differently than individuals with normal HDL-C.