Aortic tissue from seven patients with giant cell arteritis (GCA) was investigated using light microscopy and immunocytochemistry. Four surgical cases and three autopsy cases were included. All the specimens displayed a severe reduction in the size and number of media smooth muscle cells immunopositive for alpha-smooth muscle actin (alpha-SMA). A subtotal loss of alpha-SMA-positive cells was seen in non-inflamed media tissue, continuing gradually towards multiple calcified acellular lesions totally devoid of alpha-SMA immunoreactivity. There was a slight to moderate granulomatous inflammatory reaction in the tissue surrounding part of the acellular lesions. Foreign body giant cell reaction and elastin degradation were found at the ends of the acellular calcified areas. The present findings indicate that the atrophy and the loss of alpha-SMA-positive cells in the aortic media in GCA is primary, and that the granulomatous reaction is secondary and directed against atrophic calcified media tissue.