Amino acid sequence analysis of a b4 light chain from a rabbit homogeneous antistreptococcal antibody revealed the presence of two amino acid substitutions in the constant region not previously reported for these positions. These interchanges, consisting of serine for alanine at position 121 and leucine for glutamine at position 124, were also present in about 30% of the pooled b4 light chains isolated from pooled IgG from the rabbit (4539) that produced the homogeneous antibody. In addition, these interchanges (b4var) were found, always at the same levels, in varying percentages in nonimmune or early immune bleedings from related rabbits in this pedigreed family and could be traced for five generations. The inheritance pattern of b4var was consistent with autosomal codominant inheritance.