Interleukin 4 (IL-4) gene expression is controlled at the level of transcription by the complex interactions of multiple factors that bind to a proximal promoter region. Nuclear factor of activated T cells (NFAT) can bind up to five purine-rich sequences in the IL-4 promoter termed the P elements (P0-P4). In this paper, we characterize a novel P element in the upstream region of the human IL-4 promoter that me term P5. P5 shares a core NFAT motif ((-353)GGAAA(-357)) and additional sequence similarity with the other P elements and supported strong interactions between the NFATp DNA-binding domain (DBD) and the AP-1 proteins cFos and cJun in DNA-binding assays. Inducibility of the IL-4 promoter was significantly impaired in a reporter construct in which the P5 element was mutated in the context of the full-length promoter. We conclude that PS represents a novel IL-4 promoter P element that contributes to IL-4 promoter inducibility.