In order to elucidate the role of NF-ATp, one of the most prominent members of family of NF-AT transcription factors in peripheral T lymphocytes, in T cell activation and differentiation we created NF-ATp-deficient mice by gene targeting. Such NF-ATp-/- mice are born and appear to develop a normal immune system. Apart from clear-cut defects in the synthesis of mRNAs for Th2-type lymphokines, such as IL-4, IL-5, IL-10 and IL-13, in primary and secondary stimulations of spleen cells in vitro, of a distinct impaired deletion of V beta 11+/CD4+ T lymphocytes from these mice was detected after superantigen injection. Moreover, NF-ATp-/- mice older than 6 weeks show an 2-5 fold increase in number of lymphocytes. This is correlated with an increased expression of activation markers CD44 and CD69 and decreased expression of CD62.