The expression of the αvβ3-integrin in nonproliferating vascular beds remains unclear. To determine possible organ-specific differences, we compared αvβ3-integrin expression in the lung and other organs. Paraffin-embedded tissue sections of lung, liver, brain, muscle and skin obtained from rats were processed for immunohistochemistry with a monoclonal (LM609) and a polyclonal antibody (AB1903) against the αvβ3-integrin. Immunogold electron microscopy was used to localize αvβ3-integrin in rat lung microvasculature. With the use of custom-designed primers, lung sections were subjected to in situ PCR in a thermal cycler to amplify αvor β3mRNA. To confirm specific amplification, PCR products were further hybridized in situ with an αvor β3cDNA probe. In the lung, the αvβ3-integrin protein as well as αvand β3mRNAs was extensively evident in the endothelium of extra-alveolar and alveolar microvessels, in vascular smooth muscle, and in large bronchial epithelium but not in the epithelium of alveolar ducts or alveoli. Ultrastructural immunogold labeling showed the presence of the integrin on the luminal and abluminal faces of the lung microvascular endothelium but not on the apical surface of the alveolar epithelium. Staining for the integrin was generally negative in blood vessels of several systemic organs, although weak staining was evident in branches of the hepatic portal vein. The constitutive presence of the αvand β3mRNAs and the αvβ3-integrin in the lung microvascular bed suggests that gene transcription for the integrin is ongoing in lung vessels. Because it binds vitronectin, the lung vascular αvβ3-integrin may play a role in ligation of bloodborne, vitronectin-containing macromolecular complexes formed in inflammation.