OBJECTIVE Clinical and epidemiological studies have reported the beneficial effects of tree nuts and peanuts on serum lipid levels. We studied the effects of consuming 15% of the daily caloric intake in the form of pistachio nuts on the lipid profiles of free-living human subjects with primary, moderate hypercholesterolemia (serum cholesterol greater than 210 mg/dL). METHODS design: Randomized crossover trial. setting: Outpatient dietary counseling and blood analysis. subjects: 15 subjects with moderate hypercholesterolemia. intervention: Fours weeks of dietary modification with 15% caloric intake from pistachio nuts. METHODS Endpoints were serum lipid levels of total cholesterol, HDL-C, LDL-C, VLDL-C, triglycerides and apolipoproteins A-1 and B-100. BMI, blood pressure, and nutrient intake (total energy, fat, protein, and fiber) were also measured at baseline, during, and after dietary intervention. RESULTS No statistically significant differences were observed for total energy or percent of energy from protein, carbohydrate or fat. On the pistachio nut diet, a statistically significant decrease was seen for percent energy from saturated fat (mean difference, -2.7%; 95% CI, -5.4% to -0.08%; p = 0.04). On the pistachio nut diet, statistically significant increases were seen for percent energy from polyunsaturated fat (mean difference, 6.5%; 95% CI, 4.2% to 8.9%; p<.0001) and fiber intake (mean difference, 15 g; 95% CI, 8.4 g to 22 g; p = 0.0003). On the pistachio diet, statistically significant reductions were seen in TC/HDL-C (mean difference, -0.38; 95% CI, -0.57 to -0.19; p = 0.001), LDL-C/HDL-C (mean difference, -0.40; 95% CI, -0.66 to -0.15; p = 0.004), B-100/A-1 (mean difference, -0.11; 95% CI, -0.19 to -0.03; p = 0.009) and a statistically significant increase was seen in HDL-C (mean difference, 2.3; 95% CI, 0.48 to 4.0; p = 0.02). No statistically significant differences were seen for total cholesterol, triglycerides, LDL-C, VLDL-C, apolipoprotein A-1 or apolipoprotein B-100. No changes were observed in BMI or blood pressure. CONCLUSIONS A diet consisting of 15% of calories as pistachio nuts (about 2-3 ounces per day) over a four week period can favorably improve some lipid profiles in subjects with moderate hypercholesterolemia and may reduce risk of coronary disease.