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Human immunoglobulin heavy chain constant region genes have been characterised in isolated clones. The human c mu gene comprises discrete domains for C mu 1, C mu 2, C mu 3 and C mu 4 + tp separated by short intervening sequences. The C delta gene has been located about 5 kb downstream of C mu 4. Furthermore, the coding segments for the membrane form of mu have been located 1.9 kb downstream of C mu 4. Tandemly repeated sequences implicated in the heavy chain class switch occur upstream of the C mu and the C gamma genes, but none were detected near the C delta gene. These tandem repeats are very homologous to those of mouse. Particularly common is the sequence G-A-G-C-T. These data suggest that the mu to gamma switch in humans involves DNA rearrangements of the CH-genes and subsequent deletion of DNA, but that the coexpression of C mu and C delta genes results from different mechanisms.