Nuts and seeds are rich in unsaturated fat and other nutrients that may reduce inflammation. Frequent nut consumption is associated with lower risk of cardiovascular disease and type 2 diabetes. The authors examined associations between nut and seed consumption and C-reactive protein, interleukin-6, and fibrinogen in the Multi-Ethnic Study of Atherosclerosis. This 2000 cross-sectional analysis included 6,080 US participants aged 45-84 years with adequate information on diet and biomarkers. Nut and seed consumption was categorized as never/rare, less than once/week, 1-4 times/week, and five or more times/week. After adjustment for age, gender, race/ethnicity, site, education, income, smoking, physical activity, use of fish oil supplements, and other dietary factors, mean biomarker levels in categories of increasing consumption were as follows: C-reactive protein-1.98, 1.97, 1.80, and 1.72 mg/liter; interleukin-6-1.25, 1.24, 1.21, and 1.15 pg/ml; and fibrinogen-343, 338, 338, and 331 mg/dl (all p's for trend < 0.01). Further adjustment for hypertension, diabetes, medication use, and lipid levels yielded similar results. Additional adjustment for body mass index moderately attenuated the magnitude of the associations, yielding borderline statistical significance. Associations of nut and seed consumption with these biomarkers were not modified by body mass index, waist:hip ratio, or race/ethnicity. Frequent nut and seed consumption was associated with lower levels of inflammatory markers, which may partially explain the inverse association of nut consumption with cardiovascular disease and diabetes risk.