Mice immunized to a syngeneic methylcholanthrene-induced fibrosarcoma by surgical removal of a growing tumor showed specific resistance to challenge with that tumor. An in vivo response to tumor-specific antigens solubilized by hypertonic potassium chloride was measured by 24-hr footpad swelling response in mice immunized to the tumor from which the antigens were extracted. Normal mice given an injection of 5 X 10(6) tumor cells showed significant 24-hr footpad swelling response to solubilized tumor antigens (solubilized from the tumor line injected) 10 days after tumor transfer. The responses were negative 28 days after tumor transfer when tumor diameters were in excess of 1.0 cm. Surgical removal of tumor at this point promptly restored footpad responses within 24 hr. The footpad response is undoubtedly a complex situation. However, continued study of this response correlated with other measures of in vitro with in vivo tumor immunity holds promise not only of understanding the nature of the footpad response itself but also of unraveling some of the immunologic mechanisms of host-tumor interactions.