The effect of diphtheria toxin on tumor cells was studied in mice with transplanted Ehrlich ascites or solid tumor. For ascites tumor, the results were assessed on the bases of the trend in body weight, the incidence of ascites on the 13th day after transplantation, and the survival time. For solid tumor, the results were assessed on the basis of the weights of the dissected tumors. The results obtained demonstrate inhibition of both ascites and solid tumors. Inhibition of ascites tumor was dose dependent but the higher doses were toxic. The treatment was most effective after i.p. administration and weakest after s.c. administration. The i.p. route permitted a highly significant increase in survival time. The effectiveness of s.c. administration was improved when a given amount of diphtheria toxin was divided over several administrations, one per day, rather than administered in a single dose. Inhibition of solid tumor by i.p., i.m., and s.c. treatment was approximately 70%. Some possible explanations for the difference in sensitivity between normal and cancer cells are discussed.