Guinea pig serum contains two isotypes of immunoglobulin G: IgG1 and IgG2. These immunoglobulins are antigentically distinct from each other and they mediate different biologic processes in the same guinea pig, although they share the ability to bind the same antigen. An attempt was made to study the primary structure of the gamma1 heavy chain from IgG1 in comparison with the largely known primary structure of the gamma-heavy chain from IgG2, with the aim of demarcating the structural differences between these molecules. IgG1 was isolated from the serum of immune strain 13 guinea pigs. Both IgG1 and the gamma1 chain were digested with CNBr. Nine fragments were isolated from both digests by gel filtration procedures before and after reductive cleavage of disulfide bonds. These fragments appear to account for the entire approximately 444 residues in the gamma1 chain. Amino acid composition data of CNBr fragments suggest that at least the amino terminal approximately 182 residues of the gamma1 and gamma2 chains are very similar. Two of the fragments which have been isolated have amino acid compositions suggesting their derivation from the "hinge" region and carboxyl terminus of the gamma1 chain.