The aim is to determine the relationship of spontaneously occurring and hemodynamically induced intimal thickening in blood vessels to the etiology of intracranial arterial ("berry") aneurysms and to the pathogenesis of atherosclerosis. Cumulative scientific evidence indicates that the pathogenesis of such aneurysms is intimately related to intimal thickening at the arterial forks of cerebral arteries. Intimal thickening, known to precede the microscopic deposition of lipid in the arterial wall, is also a prominent feature in early cerebral aneurysm formation. Recent studies suggest that hemodynamic factors are of importance in the localization of atherosclerosis in man and also in the localization of intimal thickening and lipid deposition and in the pathogenesis of intimal tears, dissection and thrombi, in formation and rupture of aneurysms and in the development of atherosclerosis in the sac walls of cerebral aneurysms. These investigations are concerned with the nature, morphology and functional characteristics of (1) spontaneously occurring intimal thickening at arterial forks and in aneurysms and (2) hemodynamically induced intimal thickening in experimentally produced aneurysms, arteriovenous fistulas, and vascular configurations. The special feature of this approach is that it is multi-faceted comprising light and electron microscopy, histochemistry, experimental microvascular surgery, the rabbit ear chamber technique and ultrasound. The results are expected to provide information of fundamental importance concerning (1) the pathogenesis of cerebral aneurysms, of intimal thickening and of atherosclerosis at vascular forks, and (2) the interrelationship of intimal thickening, atherosclerosis, thrombosis and hemodynamics.