Angiogenesis, which promotes tumor proliferation and invasiveness, is mediated by integrin-dependent cell adhesion mechanisms and requires expression of integrin alpha v beta 3. To determine whether integrin alpha v beta 3 is expressed in the small blood vessel hyperplasia characteristic of glioblastoma tumors, we explored the mRNA and protein expression of integrin alpha v, beta 3, beta 5, and beta 1 subunits in small blood vessels in gliomas of various grades and nontumorous brain biopsies. Antisense beta 3 and beta 5 riboprobes hybridized to small blood vessels (endothelial and adjacent mesenchymal cells) in 11 of 11 glioblastomas and 2 of 4 anaplastic astrocytomas, but failed to hybridize to small blood vessels in 12 non-neoplastic specimens and 4 low-grade astrocytomas. In contrast, antisense alpha v and beta 1 riboprobes hybridized to small blood vessels in all of the biopsies. The expression of integrin alpha v beta 3 protein in these vessels was determined by immunohistochemical analysis using anti-integrin subunit-specific antibodies. The findings were similar to those obtained using in situ hybridization: beta 3 subunit protein was detected on small blood vessels in 9 of 12 glioblastoma and 2 of 4 anaplastic astrocytomas, whereas it was not detected in small blood vessels of 10 non-neoplastic brains and 4 low-grade astrocytomas. In contrast, the alpha v and beta 1 subunit proteins were detected in small blood vessels in all of the brain biopsies, whereas the beta 5 subunit protein could not be detected. These data suggest that integrin alpha v beta 3 is expressed in small blood vessels of glioblastoma tumors.