Interleukin-4 (IL-4) has important regulatory functions in the immune system, particularly in the generation of immunoglobulin E, the principal mediator of allergic responses. The molecular basis of IL-4 action has remained elusive so far. Here we report on a novel human transcription factor, termed nuclear factor IL-4 (NF-IL4), which is posttranslationally activated by IL-4 in lymphoid and monocytic cells. Homologous binding sequences for NF-IL4 were identified in the promoter regions of the IL-4 controlled CD23b and I epsilon genes. We defined a palindromic 9-bp consensus sequence (5'-TYCYRRGAA-3') as IL-4-responsive element (IL-4RE). Point mutation analysis of the CD23b promoter showed that binding of NF-IL4 to the IL-4RE is essential for the initiation of gene transcription in response to IL-4. NF-IL4 was not activated by Ca2+ ionophore, phorbol ester and cAMP either alone or in combination suggesting a non classical pathway for IL-4 signal transduction.