The solid Yoshida sarcoma implanted on the feet of rats was subjected to local hyperthermia by water bath immersion. Tumor response was governed by the temperature and duration of heating (i.e., the degree of heating) and by tumor volume. With small tumors (1.0- to 1.5-ml volume) an intratumor temperature of 42 degrees maintained for 1 hr led to tumor regression in 11 to 13 days, and the tumor volume was halved every 2.6 days. Following 2 hr hyperthermia (42 degrees) the tumors disappeared in 6 to 7 days, and tumor volume was halved every 1.2 days. Tumors of 2 to 3-mol volume had left the exponential phase of the growth curve and required 2 hr at 42 degrees for cure. Following heating at 40 degrees for 1 hr, there was a 50% increase in O2 uptake and anaerobic CO2 production by the tumor, accompanied by enhanced dissemination by lymphatic, vascular, and direct routes, and tumor was found in organs not usually the site of metastases (e.g., testis and stomach). With large tumors (3.0 to 4.5 ml), the survival time of the rats was significantly reduced. These results occurred in the absence of a rise in body temperature of the animals. It is concluded that in this animal-tumor system, hyperthermia at a temperature inadequate for tumor destruction (40 degrees) can result in changes in the tumor that represent a hazard to the host.