The expression of the α_vβ₃-integrin in nonproliferating vascular beds remains unclear. To determine possible organ-specific differences, we compared α_vβ₃-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 α_vβ₃-integrin. Immunogold electron microscopy was used to localize α_vβ₃-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 α_vor β₃ mRNA. To confirm specific amplification, PCR products were further hybridized in situ with an α_v or β₃ cDNA probe. In the lung, the α_vβ₃-integrin protein as well as α_v and β₃ mRNAs 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 α_v and β₃ mRNAs and the α_vβ₃-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 α_vβ₃-integrin may play a role in ligation of bloodborne, vitronectin-containing macromolecular complexes formed in inflammation.