Brain arteriovenous malformations cause intracranial hemorrhage. Molecular characterization of lesional tissueimplicates angiogenic (vascular endothelial growth factor, ANG-2, matrix metalloproteinase-9) and inflammatory(cytokines and chemokines) pathways, but the pathogenesis remain obscure and medical therapy is lacking. Macrophageand neutrophil invasion has also been observed in the absence of prior intracranial hemorrhage. Common polymorphismsin interleukin-1_ and activin receptor-like kinase-1 are associated with arteriovenous malformationsusceptibility, and polymorphisms in interleukin-1_, interleukin-6, tumor necrosis factor-_ and APOE are associatedwith arteriovenous malformation rupture. These observations suggest that even without a complete understanding of thedeterminants of arteriovenous malformation development, the recent discoveries of downstream derangements invascular function and integrity may offer potential targets for therapy development. Furthermore, biomarkers can beestablished for assessing intracranial hemorrhage risk. Finally, these data will aid in development of model systems formechanistic testing by development of surrogate phenotypes (microvascular dysplasia) and/or models recapitulating theclinical syndrome of recurrent spontaneous intracranial hemorrhage.