AbstractVascular inflammation in giant cell arteritis is generally described as a process involving dendritic cells, T‐lymphocytes, and effector tissue macrophages. Less is known about the contribution of phagocytes that are recruited early, such as monocytes and neutrophils. These cells express and secrete pro‐inflammatory S100 proteins which directly activate endothelial cells. In this study the expression of S100A8/S100A9 and S100A12, pro‐inflammatory proteins specific for early recruited phagocytes, was studied in biopsies from 36 patients with giant cell arteritis. In addition, serum concentrations of these proteins were analysed in serum samples from 42 patients and 35 healthy controls. The S100A8/S100A9 complex was found to be abundant in the adventitia and media in affected arteries. Besides neutrophils, cells expressing these proteins belonged to a pro‐inflammatory subtype of CD68‐positive monocytes. In contrast, S100A12 expression was restricted to neutrophils that were found around the vasa vasorum within the adventitial layer. Both S100A8/S100A9 and S100A12 serum concentrations were significantly higher in patients with giant cell arteritis than in healthy controls. In conclusion, recently recruited phagocytes expressing pro‐inflammatory S100 proteins take part in the vascular inflammation of giant cell arteritis. They may play important roles at the vasa vasorum of affected vessels, which represent sites of entry for recruited inflammatory cells. These data indicate that phagocytes within the adventitia and media contribute to the process of inflammation via release of the pro‐inflammatory S100 proteins S100A8, S100A9, and S100A12. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.