Changes in susceptibility to treatment with Cytoxan, methotrexate, 5-fluorouracil, and Adriamycin, single or in combination, have been studied during the initial and progressive stages of s.c. and pulmonary (via tail vein injection) growth of two transplanted syngeneic C3H/He mammary carcinomas. One tumor was fast growing, reaching a size of 3 mm from a 1-mm s.c. implant in 7 days; the second tumor would grow to the same size in 30 days. The tumor with the slower growth rate was more susceptible to drug treatment, manifested by delayed growth as well as by prevented growth. The slower-growing tumor also remained susceptible longer, when treatment was delayed, than did the faster-growing tumor. Pulmonary growth was more often prevented by drug treatment than was s.c. growth. Tumor implants s.c. which had reached palpable size could be reduced temporarily to impalpable size by effective drug treatment but were rarely cured. The importance of early treatment relative to the time of tumor implantation was indicated when early treatment with a single drug proved more effective than did delayed treatment with a more potent combination of drugs.