To examine the effect of amino acid substitutions in lysozyme on the binding of antibodies to lysozyme, lysozyme was purified from the egg whites of California quail (Lophortyx californicus) and Gambel quail (Lophortyx gambelli). Tryptic peptides were isolated from digests of the reduced and carboxymethylated lysozymes and subjected to quantitative analysis of their amino acid compositions. The 2 proteins were identical by this criterion. Each peptide from the California quail lysozyme was then sequenced by quantitative Edman degradation and the peptides were ordered by homology with other bird lysozymes. California quail lysozyme is most similar in amino acid sequence to bobwhite quail lysozyme, from which it differs by 2 substitutions: arginine for lysine at position 68 and histidine for glutamine at position 121. California and bobwhite quail lysozymes were antigenically distinct from each other in quantitative microcomplement fixation tests; substitutions at one or both of these positions can alter the antigenic structure of lysozyme. Neither of these positions is among those claimed to account for the precise and entire antigenic structure of lysozyme. Two possible explanations for this discrepancy are discussed.