OBJECTIVE: To examine the relationship between markers of systemic inflammation and carotid atherosclerosis in patients with rheumatoid arthritis (RA) and healthy controls. METHODS: Carotid artery intima-media thickness (IMT) and carotid plaque were measured using high-resolution B-mode ultrasound in 204 patients with RA, ages 40-85, and 102 age- and sex-matched healthy persons. No subject in either group had ever smoked cigarettes. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were used to measure systemic inflammation. The relationship of the carotid artery IMT and carotid plaque to inflammation markers was examined, adjusting for age, sex, RA versus control status, and the cardiovascular (CV) risk factors hypercholesterolemia, systolic blood pressure, diabetes mellitus, and body mass index (BMI). RESULTS: A significant linear trend for increased carotid artery IMT was associated with increasing ESR and CRP categories (r = 0.16, P = 0.004 for ESR, and r = 0.13, P = 0.02 for CRP). These trends did not differ among RA cases and controls, and were independent of age, sex, and CV risk factors. The difference in carotid artery IMT between the lowest and highest categories of ESR was 0.221 mm (95% confidence interval [95% CI] 0.767-1.020, P = 0.02). The difference between extreme CRP categories was 0.275 mm (95% CI 0.039-0.509, P = 0.02). Both remained significant after CV risk factor adjustment. Carotid plaque displayed a similar relationship to markers of inflammation. CONCLUSION: Increased carotid artery IMT and the presence of carotid plaque are associated with markers of systemic inflammation in patients with RA and in healthy subjects. This observation is consistent with hypotheses that assign a role to systemic inflammation in atherosclerosis, and may have implications regarding RA and other chronic inflammatory diseases.