Internalization of IL-2 is important for its biological activities. The internalization of IL-2 was regulated by the duration of glutathione (GSH) treatment in CTLL-2 and CT-4R cells. Flow cytometric studies showed that the level of surface IL-2 receptors was not increased by GSH treatment. Northern blot analysis showed that the mRNA of IL-2Rp55 and IL-2Rp70, the two major components of the high-affinity IL-2 receptors, was increased 6 hr after GSH treatment. The appearance rate of membrane IL-2 receptors in GSH-treated cells was faster than that of the untreated cells. GSH also shortened the half-life (from 5 to less than or equal to 3 hr) and thus increased the turnover of the surface high-affinity IL-2 receptors. These results suggest that although GSH does not affect the level of surface IL-2 receptors, GSH may regulate the internalization of IL-2 by enhancing the synthesis and turnover of surface IL-2 receptors.