Changes in lipoprotein characteristics, such as particle size and number, may contribute to our understanding of the biochemical pathways that are influenced by exercise and niacin therapy to ameliorate secondary dyslipidemias. PURPOSE: Our purpose was to characterize changes in lipoprotein characteristics after single episodes of aerobic exercise conducted before and after 6 wks of niacin therapy in men with metabolic syndrome. METHODS: Thirteen men (44 + 7 yrs; BMI = 34.5 + 3.4 kg·m²; % fat = 35 + 5; VO2max = 27.7 + 5.1 mL·min^-1·kg^-1; waist circumference = 108.8 + 8.2 cm; HDL-C = 39 + 8 and triglycerides = 287 + 96 mg/dL; HOMA score = 4.4 + 2.0) expended 500 kcals by treadmill walking at 65% of VO2max before and after a 6-wk regimen of prescription niacin. Niacin doses were titrated by 500 mg/wk from 500 to 1500 mg/dy and maintained at 1500 mg/dy for the last 4 wks. Fasting blood samples were collected before and 24 hr after each exercise session for blood lipid and NMR analyses of lipoprotein characteristics (Lipoprofile®, Liposcience Inc., Raleigh, NC). Changes in lipid concentrations and lipoprotein particle size and number were determined by paired t-tests and multiple 1 (group) by 4 (condition) repeated-measures ANOVAs. RESULTS: A 12% reduction in cholesterol, a 34% reduction in triglyceride and an 18% increase in HDL-cholesterol were observed after six weeks of niacin therapy (p < 0.018 for all). Niacin, but not exercise, reduced total LDL particle number by 11% (p = 0.009). The reduction in LDL particle number with niacin was observed across small LDL subclasses (16 to 23%, p < 0.0032 for all) but not in the number of large LDL particles. The combination of exercise and niacin therapy reduced mean VLDL particle size 7% (p = 0.035) and the increase in mean LDL particle size approached statistical significance (p = 0.081). Participants' body weight and characteristics of VLDL, IDL, and HDL particles remained unchanged from baseline (p > 0.05 for all). CONCLUSIONS: The therapeutic effects of niacin include reducing LDL particle number - particularly in smaller, more atherogenic LDL subclasses. Moderate-intensity aerobic exercise in combination with niacin reduces mean VLDL particle size, an effect that may contribute to reductions in smaller LDL particles and triglyceride concentrations and to elevations in HDL-cholesterol.