Interleukin-4 (IL-4) is an immunoregulatory cytokine produced by activated T lymphocytes to promote the growth and differentiation of cells that participate in immune defense. This study demonstrates the rapid activation of a specific DNA binding factor by IL-4. The IL-4 nuclear-activated factor (IL-4 NAF) appeared within minutes of IL-4 stimulation and recognized a specific DNA sequence found in the promoters of IL-4-responsive genes. Activation of this putative transcription factor required tyrosine phosphorylation, and antibodies specific for phosphotyrosine recognize the IL-4 NAF-DNA complex. Thus, IL-4 appears to transduce a signal to the nucleus through tyrosine phosphorylation of a latent DNA binding factor.