The pre-TCR, which is minimally composed of the TCR g chain, the pre-T § chain, and the CD3 complex, regulates early T cell development. The pre-T § chain is a 33-kDa type I trans-membrane glycoprotein with an extracellular part similar to the constant domain of the immunoglobulin supergene family. We have sequenced (11 kb) the human pT § gene, which like the murine pT § gene consists of four exons: exon 1 encodes the 5' untranslated region, the leader peptide and the first three amino acids of the mature protein, exon 2 the extracel-lular immunoglobulin (Ig)-like domain, exon 3 a 15-amino acid peptide including a cysteine required for heterodimerization with TCR g , exon 4 the transmembrane region, the cytoplas-mic tail and the 3' untranslated sequence. The human pT § gene is located on chromosome 6p21.3, close to the HLA-A locus. Reverse transcription-PCR studies with human thymus and leukemic cells showed that alternative splicing produces a shorter pT § isoform, which lacks the Ig-like domain but contains the transmembrane elements and the extracytoplas-mic cystein and which could thus permit pairing with TCR g chain and association with CD3 molecules. The conserved splice sites suggest a yet ill-defined biological function of the short pT § protein.