Stereotactic radiosurgery effectively obliterates many arteriovenous malformations (AVMs). Hemodynamic changes in AVMs after radiosurgery have been illustrated using magnetic resonance imaging and angiography, but there have been no detailed reports describing the underlying histopathological changes. This study examines AVMs at various times after gamma knife radiosurgery (GKRS) and describes the histopathological changes that lead to vessel occlusion. The authors examined nine AVM specimens obtained 10 months to more than 5 years after GKRS, by using routine histopathological stains as well as immunohistochemical techniques to detect smooth-muscle actin, factor VIII, and type IV collagen. Blood vessels within the AVMs showed progressive changes leading to narrowing or obliteration of the lumen. The earliest changes after gamma knife irradiation appear to be damage to endothelial cells, followed by progressive thickening of the intimal layer caused by proliferation of smooth-muscle cells that elaborate an extracellular matrix that includes type IV collagen. Finally, cellular degeneration and hyaline transformation occur. For statistical correlation analyses, the specimens were graded according to the degree of histopathological change and the relative number of vessels showing such changes. Both of these parameters were significantly correlated with time after GKRS and with AVM size reduction shown on follow-up imaging studies. Gamma knife radiosurgery of AVMs causes endothelial damage, which induces the proliferation of smooth-muscle cells and the elaboration of extracellular collagen by these cells, which leads to progressive stenosis and obliteration of the AVM nidus. This series of pathological changes in AVMs after GKRS is essentially similar to the response-to-injury model of atherosclerosis.