Murine T cells and T cell lines bearing high- and low-affinity receptors for interleukin (IL) 2 were chemically cross-linked to radiolabeled IL 2 and subjected to differential detergent extractions to evaluate the extent of IL 2 receptor association with the nonionic detergent-resistant framework of the plasma membrane. Low-affinity receptors were readily solubilized by nonionic detergent extraction of whole cross-linked cells, while solubilization of high-affinity receptors required a stronger ionic detergent suggesting their association with a membrane structure that is resistant to nonionic detergents. To achieve physical separation of low- and high-affinity receptors, cells cross-linked to 125I-labeled IL 2 were centrifuged through a sucrose barrier containing Triton X-100. Alternatively, Triton X-114 extracts of plasma membrane fractions were partitioned into aqueous and detergent phases. By either approach, high-affinity receptors differed from low-affinity ones by their increased density and consisted of detergent-resistant complexes containing p55-p75 heterodimers. The low-affinity receptors, on the contrary, were of low density and consisted exclusively of detergent-soluble p55 subunits. High density and resistance to nonionic detergent extraction of high-affinity IL 2 receptors suggest their integration into lateral microdomains of the detergent-resistant framework of the plasma membrane.