Partial amino-terminal sequences of 6γ, 5μ and 2α human Ig heavy chains not previously described, are presented. These sequences in conjunction with data on 28 other heavy chains permit further definition of heavy chain variable region subgroups. The most frequently studied subgroup (I) appears to be associated with all or most classes of heavy chains for which there are sufficient data. There is one subgroup (IV) which seems only to be associated with μ chains.