The nuclear factor of activated T cells (NFAT) group of transcription factors is retained in the cytoplasm of quiescent cells, NFAT activation is mediated in part, by induced nuclear import, This process requires calcium-dependent dephosphorylation of NFAT caused by the phosphatase calcineurin, The c-Jun amino-terminal kinase (JNK) phosphorylates NFAT4 on two sites, Mutational removal of the JNK phosphorylation sites caused constitutive nuclear localization of NFAT4, in contrast, JNK activation in calcineurin-stimulated cells caused nuclear exclusion of NFAT4. These findings show that the nuclear accumulation of NFAT4 promoted by calcineurin is opposed by the JNK signal transduction pathway.