Interleukin 4 (11,4)-induced IgE production coincides with the appearance of the 2.2-kb productive ε-mRNA, but is preceded by synthesis of a 1 .7-kb ε-RNA. Analysis of cDNA copies of the 5' end of this RNA indicated that the 1.7-kb ε-RNA is a germline e immunoglobulin heavy chain transcript with an exon mapping 5' to the switch region. Transcription through switch regions has been implicated in the control of class switching. However, IL4 or cloned CD4+ T cells were able to induce germline e transcripts without inducing IgE synthesis, for which both signals were required. These results indicate that induction of human germline ε-RNA does not necessarily result in IgE synthesis, and that additional regulatory mechanisms are involved in class switching. © 1990, Rockefeller University Press., All rights reserved.