A study was made of the effect of combined adriamycin and hyperthermic treatment in a solid mouse mammary carcinoma in vivo. This study demonstrated: (a) that, when given separately, adriamycin and hyperthermia enhance the destruction of a solid mouse mammary carcinoma in vivo; hyperthermia (40.5-42.5 degreesy greatly increases tumor destruction and, in a number of cases, caused initial and long-time regression; (c) that whole-body hyperthermia in combination with adriamycin gives a significant delay in tumor growth as compared with the controls, but not to the same degree as the local combined therapy; and (d) that treatment with local hyperthermia and adriamycin gives a pronounced decrease in the lethal toxicitity of adriamycin. The effect of adriamycin and heat treatment may be due to hyperthermic cell destruction in the central area of the solid tumor, together with a synergistic effect of heat and adriamycin on the proliferating peripheral tumor cells. Furthermore, local heat application may increase the adriamycin concentration in the heated tumor area, which causes a high destructive effect and a less toxic influence on the nonheated normal tissue.