Immunochemical methods were used to test whether vitronectin receptors exist in synaptosomal membranes (SPMs) and hence are positioned to play a role in synaptic adhesion. Antibodies against the alpha v beta 3 integrin detected proteins in brain homogenates that correspond to conventional integrin subunits. Conversely, these antigens were not found in SPMs prepared from the same brain tissue. The antibodies did, however, express strong immunoreactivity towards a 27 kDa polypeptide that was greatly concentrated in SPMs from major brain regions and that was not found in tissues other than brain. This is an example of an integrin epitope contained in a synaptic polypeptide that is too small to be a conventional matrix receptor, thus, suggesting the possibility that synaptic adhesion involves unusual proteins.