CD4(+) T cells express IL-2 receptor complexes to the same level as CD8(+) T cells when the two T cell populations were stimulated simultaneously. However, the activation of downstream signaling molecules, such as Jaks, was increased in CD8(+) T cells. Although equivalent amounts of CD45, which acts as a Jak phosphatase, was expressed on the two T cell populations, those on the CD8(+) T cells have less protein tyrosine phosphatase activity than those on the CD4(+) T cells. Furthermore, we find that different CD45 isoforms dominate in the two populations; CD45RO on proliferating CD4(+) T cells and CD45RBC on proliferating CD8(+) T cells. In addition, NIH3T3 cells expressing the CD45RBC transgene had more phosphorylated Jak1 and grew faster than those with the CD45RO transgene. Thus, the expression of specific CD45 isoforms on T cells correlates with their proliferative response to IL-2, suggesting that controlling cells expressing specific CD45 isoforms could correct excessive or insufficient immune responses.