The cerebral arteries in seven cases of Moyamoya disease, demonstrated by angiography were observed by light, transmission and scanning electron microscopy. In two cases, the lumen of the terminal portion of the internal carotid artery was completely occluded by proliferated connective tissue. The characteristic pathologic change was extensive destruction of the smooth muscle cells and the elastica interna. Degeneration and necrosis of smooth muscle cells were obvious in the media. Many condensed organelles and other elements of cellular destruction were dispersed throughout the interstitium. The media was thinned. The proliferated smooth muscle cells in the intima showed the same destructive changes as in the media. The elastica interna was excessively infolded and was thickened or thinned, disrupted or disintegrated in some segments. Identical, but less severe and more localized changes were seen in three middle cerebral arteries (M2 and M5 segments) and two collateral arteries at the base of brain. These changes suggest that Moyamoya disease is a progressive disorder characterized by repeated destruction of smooth muscle cells occuring over a long time period. The pathogenesis of these changes is discussed.