IL-6 serum levels are increased in patients suffering from GCA, and this cytokine may play a role in the systemic symptoms associated with this disease. We analyzed by in situ hybridization and immunohistochemistry whether IL-6 production originates from arterial granulomas in GCA. Seven arterial biopsy specimens taken from patients with histologically proved GCA were studied. IL-6 production was detected in all cases at both the mRNA and the protein levels. IL-6-producing cells were distributed in the intima, in the media, and in the adventitia. Positive cells were clearly enriched in the media, however, and particularly in contact with the internal elastic lamina. The morphology of the IL-6-producing cells showed that they belonged to several cell populations. In the media, most IL-6-producing cells were macrophages, whereas fibroblasts also produced IL-6 in the intima. Neither endothelial cells nor giant cells were found to express the IL-6 gene. Increased IL-6 serum concentrations returned to normal levels in most patients after administration of corticosteroids, indicating that inhibition of IL-6 production by GCA granuloma cells may be one of the mechanisms of action of corticosteroids in this condition. Production of IL-6 in abnormal arteries may thus participate to the systemic manifestations of GCA.