Brain arteriovenous malformations (BAVMs) are an important cause of intracranial hemorrhage (ICH) in young adults. A small percent of BAVMs is due to hereditary hemorrhagic telangiectasia 1 and 2 (HHT1 and 2), which are caused by mutations in two genes involved in transforming growth factor-β signaling: endoglin (Eng), and activin-like kinase 1 (Alk1). The BAVM phenotype has incomplete penetrance in HHT patients, and the mechanism is unknown. We tested the hypothesis that a “response-to-injury” triggers abnormal vascular (dysplasia) development, using Eng and Alk1 haploinsufficient mice. Adeno-associated virus (AAV) expressing vascular endothelial growth factor (VEGF) was used to mimic the injury conditions. VEGF overexpression caused a similar degree of angiogenesis in the brain of all groups, except that the cortex of Alk1^+/− mice had a 33% higher capillary density than other groups. There were different levels of cerebrovascular dysplasia observed in haploinsufficient mice (Eng^+/− > Alk1^+/−), which simulates the relative penetrance of BAVM in HHT patients (HHT1 > HHT2). Few dysplastic capillaries were observed in AAV-LacZ-injected mice. Our data indicate that both angiogenic stimulation and genetic alteration are necessary for the development of vascular dysplasia, suggesting that anti-angiogenic therapies might be adapted to slow the progression of the disease and decrease the risk of spontaneous ICH.