We have identified a region of the human TNF‐α promoter between nucleotides ‐323 and ‐285, capable of influencing transcriptional activity. This region encompasses the ‐308 polymorphism and contains a 10 bp sequence homologous to the consensus binding site of activator protein‐2 (AP‐2). Protein complexes derived from U937 and Jurkat cells were found to bind to this element. Competitive EMSA using a consensus AP‐2 oligonucleotide indicated that AP‐2 may be involved. Functional assays demonstrate that this region can repress activity of a heterologous promoter in the Jurkat T‐cell line, but act as an inducible enhancer of transcription in U937 cells.