Earlier publication suggested that IgG2a and IgG2c (coding for Igh-1a and Igh-1b) are organized in tandem on the same chromosome as two distinct loci in mice. Our data suggest that IgG2a and IgG2c are not physically linked on the chromosome and are allelic – single locus in majority strains of mice. In another word, IgG2b–IgG2c–IgG2a haplotype proposed by Morgado et al. (1989) may exist in some strains of mice, but IgG2b–IgG2a and IgG2b–IgG2c are likely to be most common haplotypes in mice. Therefore, inbred mice may produce different IgG2a isotypes dependent on their origin (strain); C57B/6 and SJL mice secrete IgG2c while NMRI and DBA/2 mice secrete IgG2a only. The situation is more complicated for Swiss Webster mice (outbred) and Alzheimer's disease transgenic (AD/Tg) mice with multi-genetic backgrounds; mice may secrete only IgG2a, or IgG2c, or both IgG2a and IgG2c. IgG2a and IgG2c likely have different immune profile (response, immune-decoration) in mice due to their divergence of protein sequence. If antibodies based on IgG2a (or IgG2c) are used in chronic studies for preclinical evaluation of antibody efficacy, characterization of IgG2a isotypes in advance becomes critical in the design of such biopharmaceutical projects in order to avoid immune response.