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. Measures of Outcome: 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. CONCLUSION: 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.