The effectiveness of treatment with cyclophosphamide, methotrexate and 5-fluorouracil was studied during the s.c. and pulmonary growth of syngeneic C3H/He mammary carcinomas. Treatments with cyclophosphamide, methotrexate and 5-fluorouracil during the primary induction of immunity against a mouse mammary carcinoma inhibited the growth of the tumor, but also inhibited the development of an effective immune resistance against subsequent implants of the same tumor. However, drug treatments of mice with established tumor immunity gave added benefit without detectable depression of immune resistance.