We report the nucleotide sequence of a gene encoding the constant region of a human immunoglobulin gamma 4 heavy chain (C gamma 4). These data represent the first complete sequence determination of a human CH gene. As expected from structural studies of mouse C gamma genes, the coding sequences for the CH domains and hinge segment are separated from one another by intervening DNA sequences. Comparison with genomic sequences of the mouse C gamma 1, C gamma 2a, and C gamma 2b genes shows conservation of the sequences in the constant region domains and the 3' untranslated region surrounding the presumed site of poly(A) addition.