Elevated pulse pressure has been associated with an increased risk of cardiovascular disease, which is increasingly being seen as an inflammatory disease. Thus, the mechanism underlying the link between elevated pulse pressure and cardiovascular disease risk may be inflammation. However, investigators have not examined the relationship between pulse pressure and C-reactive protein, an inflammation marker that has been closely linked to cardiovascular risk. We examined the cross-sectional relationship between pulse pressure and C-reactive protein among 9867 healthy persons 17 years of age or older who participated in the Third National Health and Nutrition Examination Survey. The association between pulse pressure and the odds of having an elevated C-reactive protein level (> or = 0.66 mg/dL) was assessed by logistic regression. In a model that adjusted for systolic blood pressure, demographic factors, cholesterol, measures of obesity, smoking, alcohol consumption, physical activity, and antihypertensive medication use, a 10 mm Hg increase in pulse pressure was associated with a 15% increase in the odds of having an elevated C-reactive protein level (odds ratio, 1.15; 95% confidence interval, 1.01 to 1.31; P=0.04). When the same model was re-run adjusting for diastolic blood pressure instead of systolic blood pressure, a 10 mm Hg rise in pulse pressure was associated with a significant 12% increase in the odds of having an elevated C-reactive protein level. Systolic and diastolic blood pressure were unrelated to C-reactive protein once pulse pressure had been accounted for. Our results suggest that increases in pulse pressure are associated with elevated C-reactive protein levels among apparently healthy US adults, independent of systolic and diastolic blood pressure.