Using a monoclonal antibody, SB1 38.456, raised against chicken neuronal Thy-1, we have shown that a significant amount of Thy-1 is associated with the non-ionic detergent-insoluble fraction of chicken brain membranes. Furthermore, this population of Thy-1 is not released by any biochemical method which disrupts microfilaments, microtubules or intermediate filaments, but is released by raising the temperature to 40°C in high ionic strength, cation-containing buffer. We propose, therefore, that a population of Thy-1 molecules is associated with the cytoskeleton either via a linker protein or via other cell surface glycoproteins which are directly associated with the cytoskeleton.