We have determined the amino acid sequence of the first constant (C) region domain (C delta 1) and the hinge region of the delta heavy chain of human IgD WAH and also the sequence of the adjacent COOH-terminal portion of the variable (V) region, including the JH region. Together with the sequence of the Fc fragment already reported, this establishes the complete amino acid sequence of the C region of the human delta chain and confirms the presence of three C region domains in human IgD. Although the CH1 domains of the five classes of human heavy chains have the expected degree of homology (approximately 30%), the homology of the C delta 1 domains of the human and mouse chains is less than that exhibited by the CH1 domains of other pairs of human and mouse heavy chains. The hinge region of the human delta chain has an unusual structure; the NH2-terminal half has four (or five) GalN oligosaccharides attached, whereas the COOH-terminal half lacks carbohydrate, is dissimilar in sequence, and has a high charge. A computer search verified that the GalN-rich segment has a high degree of identity in sequence with the middle portion of the human C mu 2 domain and that the high-charge segment is related to the same sequence. We propose that the two segments of the human delta hinge have a common evolutionary origin and arose by duplication and independent mutation of a hinge exon derived from the ancestral gene for the C mu 2 domain.