BACKGROUND: Fluorine-18-labelled fluoroxdeoxyglucose (FDG) positron emission tomography (PET) has been used to evaluate atherosclerotic plaque metabolic activity, and through its uptake by macrophages is believed to have the potential to identify vulnerable plaques. The aims were to compare FDG uptake in carotid plaques from patients who had sustained a recent thromboembolic cerebrovascular event with that in femoral artery plaques from patients with leg ischaemia, and to correlate FDG uptake with the proportion of M1 and M2 macrophages present. METHODS: Consecutive patients who had carotid endarterectomy for symptomatic, significant carotid stenosis and patients with severe leg ischaemia and significant stenosis of the common femoral artery underwent FDG-PET and histological plaque analysis. The voxel with the greatest activity in the region of interest was calculated using the Patlak method over 60 min. Plaques were dual-stained for CD68, and M1 and M2 macrophage subsets. RESULTS: There were 29 carotid and 25 femoral artery plaques for study. The maximum dynamic uptake was similar in carotid compared with femoral plaques: median (range) 9.7 (7.1-12.2) versus 10.0 (7.4-16.6) respectively (P = 0.281). CD68 macrophage counts were significantly increased in carotid compared with femoral plaques (39.5 (33.9-50.1) versus 11.5 (7.7-21.3) respectively; P < 0.001), as was the proportion of M1 proinflammatory macrophages. The degree of carotid stenosis correlated with the maximum dynamic FDG uptake (rs = 0.48, P = 0.008). CONCLUSION: FDG uptake was no greater in symptomatic carotid plaques than in the less inflammatory femoral plaques. In patients on statin therapy. FDG uptake occurred in areas of significant arterial stenosis, irrespective of the degree of inflammation.