Abstract The 5A11 antigen is the avian homologue of a developmentally regulated 45-kDa glycoprotein of the immunoglobulin super-gene family implicated in heterotypic cell-to-cell interactions. Employing chemical cross-linking agents, we provide evidence for oligomerization of the 5A11 antigen in Triton X-100-solubilized preparations of neural retina, liver, and erythrocytes and in intact erythrocytes. Dimerization was demonstrated through partial proteolytic digestion and diagonal gel electrophoresis. Sedimentation velocity separation demonstrated that the 5A11 dimer, derived from retina, is part of a larger macromolecular complex characterized by a sedimentation rate comparable to that of the glutamine synthetase octomer (S = 15.2). In contrast, the sedimentation velocities of the dimer and monomer from erythrocytes were similar. These data provide the first biochemical evidence of interaction of the 5A11 antigen and differences in these interactions between tissues.