Risk factors for the development and rupture of intracranial saccular (berry) aneurysms were identified in a case-control study of autopsy subjects. The development of berry aneurysms was positively correlated with increased frequencies of systemic arterial hypertension (p less than 0.001), cerebral artery atherosclerosis (p less than 0.05), and marked asymmetry of the cerebral vessels comprising the circle of Willis (p less than 0.005). In addition, patients with berry aneurysms more frequently had histories of persistent headache (p less than 0.001), pregnancy-induced hypertension (p less than 0.01), long-term use of analgesics (p less than 0.001), especially aspirin (p less than 0.05), and a family history of stroke (p less than 0.05). Factors associated with a decreased risk of berry aneurysms included treatment with insulin to control diabetes mellitus (p less than 0.005), leanness (p less than 0.05), chronic pancreatitis (p less than 0.001), malignant tumors (p less than 0.001), and moderate or severe coronary or renal atherosclerosis (p less than 0.05). Rupture of berry aneurysms was positively correlated with size (p less than 0.05) and the presence of multiple aneurysms (p less than 0.005), but also with long-term analgesic usage (p less than 0.05), excessive ethanol consumption (p less than 0.01), and fatty metamorphosis of the liver (p less than 0.01). The factors that predispose to rupture of berry aneurysms are interrelated in the sense that several of them are known to cause a decrease in the synthesis of prostaglandin E, whereas one of the factors that appears to be protective has the opposite effect. Marked and abrupt lowering of serum prostaglandin levels would cause dilatation of cerebral vasculature and increased cerebral blood flow; in the setting of hypertension, focal defects in cerebral arteries could develop, leading to the formation and subsequent rupture of berry aneurysms.