The gamma chain of human fibrinogen has been shown to be heterogeneous; three forms of various sizes are normally present in plasma. To further characterize the two less prevalent elongated variants, we have purified the three forms of the gamma chain, isolated unique tryptic fragments, and sequenced the variant portions of each chain. The intermediate-sized form (gamma 55) has a sequence identical to the longest variant (gamma 57.5) from residue Val-408 to Pro-423, which is the C terminus of the gamma 55 chain. The gamma 57.5 chain extends an additional four amino acids. The C-terminal amino acid sequence and corresponding nucleotide sequence of the gamma 55 chain show marked similarity with an elongated gamma-chain variant of rat fibrinogen. In addition, a remarkable similarity in both amino acid and nucleotide sequence was noted between the human gamma 55 chain and the C-terminal extension in human and bovine A alpha chain of fibrinogen, which are encoded by the cDNA but are posttranslationally cleaved and are not found in plasma. The findings suggest an evolutionary conservation in the C-terminal amino acid sequence found in both the fibrinogen A alpha and gamma chains in several species.