The antitoxin response of isogenic mice (inbred strains and F1 hybrids), immunized with diphtheria and tetanus reference vaccines, was compared with the response of animals from an NIH outbred stock. The variance in antitoxin response was smaller within the groups of isogenic mice than within the group of mice from the outbred strain. The case for estimating the potency of diphtheria and tetanus vaccines by using isogenic mice is discussed. It is concluded that the general introduction of one common inbred strain or F1 hybrid selected on the basis of sensitivity would increase the comparability of data between laboratories and would enable an estimated reduction in the use of animals of about 35% or an improvement in the precision of the estimate of potency.