We have isolated an antibody population which reacts with hemoglobin S but not with hemoglobin A. These proteins differ by a single amino acid substitution. We have isolated an antibody population which reacts with human cytochrome c but not with monkey cytochrome c. These proteins also differ by a single amino acid residue. These antibody populations react with their specific antigens with a stoichiometry of one antibody combining site per asymetrical antigenic unit. A second, different antibody population which also reacts with human cytochrome c with a stoichiometry of unity has been isolated by virtue of its excess production. The kinetics of reaction of these site specific antibody populations indicates considerable homogeneity. This study represents the first isolation of antibodies specific to single chemical modifications of globular proteins and the first demonstration of a one to one binding stoichiometry between such an antigen and an antibody population.