We have characterized the structure of the human immunoglobulin C alpha 1 and C alpha 2 germ-line transcripts that are synthesized upon treatment of human B lymphocytes with Branhamella catarrhalis (a B cell mitogen) and transforming growth factor beta 1 (TGF-beta 1). These transcripts initiate upstream of the switch alpha 1 and switch alpha 2 regions and contain, together with the C alpha 1 and C alpha 2 sequences, additional exons designated according to the generally accepted nomenclature I alpha 1 and I alpha 2 respectively. The I alpha exons are spliced directly onto the acceptor splice site of the CH1 domains of the C alpha 1 and C alpha 2 genes. As in other previously characterized germ-line transcripts, stop codons present in all three reading frames prevent translation of the C alpha 1 and C alpha 2 heavy-chain coding sequences. The longest open reading frame (ORF) present in the I exons can code for a polypeptide of only 26 amino acids. The human I alpha exons do not show any significant sequence homology with the corresponding mouse I alpha exon. However, comparison of nucleotide sequences of the genomic mouse and human I alpha regions demonstrated the presence of an approximately 300 bp highly conserved element located immediately upstream of the transcription initiation sites of the human and mouse C alpha germ-line transcripts. The isolation of the C alpha 1 and C alpha 2 germ-line transcripts will further facilitate the characterization of the molecular events responsible for the regulation of the human C alpha heavy chain loci.