The complete amino acid sequence of the murine gamma 2a heavy chain CBPC-101 Fc region of allotype Ig1b was determined by automated and manual Edman degradation procedures. Both chemical and enzymatic cleavages were used to obtain peptides which were purified by gel filtration followed by high-pressure liquid chromatography. The sequence was in good agreement with that predicted from the nucleotide sequence of a gamma 2a gene of allotype Ig1b except for two positions. Comparison with published data on MOPC 173 gamma 2a heavy chain of allotype Ig1a revealed 8 amino acid substitutions in the CH2 domain (7% differences) and 18 substitutions (27%) in the CH3 domain. Many of the observed interchanges occur at positions at which murine heavy chains of other classes also differ from the gamma 2a chains. Our data suggest that the divergence of the gamma 2a Ig1a gene found in BALB/c mice and of the gamma 2a Ig1b gene found in CB 20 mice must have occurred long ago and that the CH2 domain was much more conserved than the CH3 domain.