Summary and Conclusions The decay of circulating diphtheria antitoxin in the guinea pig was determined from measurements of the loss of passively transferred homologous antibody. The experiments were carried out in normal guinea pigs of different strains and ages and in irradiated animals. The disappearance of the antitoxin was followed by either immunological titration of Lr units or radioactivity determinations of antitoxin trace-labeled with I131. Essentially identical rates of antitoxin elimination were observed under the various experimental conditions tested and with both methods of measurement. The average value obtained for the biological half-life of diphtheria antitoxin was 5.9 ±0.2 days. This result indicated that antitoxin, like homologous γ globulin, is catabolized at a relatively slow rate in the guinea pig. The use of the decay data in the kinetic analysis of antitoxin formation in the guinea pig is discussed.