Immunoglobulin class switching is characteristic to the tetrapod lineage, but the nature of this process has been elucidated only in mammals, where I-exon transcription initiates and directs the recombination in the IgH locus. Here, it is shown that an I-exon occurs 5' of the nu (IgY constant region) gene of the duck (Anas platyrhynchos): it is longer than mammalian I-exons and comprised primarily of tandem repeats. The Inu promoter was identified and shown to be responsive to stimulation with IL-4 but not LPS. It contains Oct, LYF-1, ATF, and C/EBP motifs. Site directed mutagenesis indicates that 2 C/EBP motifs are uniquely necessary for the response of the promoter to IL-4, as tested in the mouse pre-B cell line, 70Z/3. These results support the conclusion that the signal transduction pathways controlling I-exon promoter responses to cytokines have been highly conserved in vertebrate evolution.