DNA-protein binding studies and trans-activation assays in the Xenopus oocyte were used to assess the presence and functional state of factors controlling interleukin 2 (IL-2) transcription in primary human T-lymphocytes. The work summarized here shows that in resting naive CD4⁺/CD45Ro^-T cells, the IL-2 promoter is repressed by a silencer bound to a purine-rich element (Pud or NFAT binding site). Upon first mitogenic stimulation of these cells, a positive transcription factor (activator) is synthesized and activates the IL-2 gene by binding to the Pud element. In memory CD4⁺/CD45RO⁺ cells, the silencer does not reappear and IL-2 transcription is controlled exclusively by the transition from inactive to active state of the activator correlated with its cytoplasmic or nuclear location. In addition, we show that differences in size and function exist between the Pud-factors that regulate the IL-2 gene in normal T cells and in tumor cell line models such as the human leukemia Jurkat and the mouse thymoma EL4.