We elucidated a series of alternatively spliced human ε mRNAs by employing a human ε-specific RT-PCR strategy. Two mRN A isoforms provide for the expression of distinct membrane IgE proteins, the common form of which contains a novel 56-amino-acid sequence after the last ε constant-region domain. Other mRNAs encode, in addition to the classic secreted ε chain, at least three novel ε secreted proteins that lack a transmembrane domain and possess distinctive C-terminal features. Furthermore, the expression of these ε mRNA isoforms is differentially regulated by stimuli such as interleukin-10, FcεRII cross-linking and aromatic hydrocarbons found in diesel exhaust.