A variant of the MPC 11 cell line, M 311, produces a short immunoglobulin heavy chain. When compared with the parental gamma 2b heavy chain, M 311 was found to have a carboxyl terminal deletion comprising the CH3 domain. The COOH-terminal cyanogen bromide (CNBr) cleavage fragment of M 311 is identical to a corresponding segment ofa parental heavy chain CNBr fragment, with the exception of a substitution of asparagine for lysine at the COOH-terminal residue. This observation enabled prediction of both the parental DNA sequence in this region and the genetic mechanism which generated the variant, a frameshift followed by premature termination. This hypothesis is supported by studies of the DNA sequence of the MPC 11 gamma 2b constant region gene.