The effects of step-up (42----44 degrees sequence) and step-down (44----42 degrees sequence) heating were studied on a transplantable mammary adenocarcinoma of C3H/He mouse. Tumor-bearing legs were immersed in a water bath and the response to hyperthermia was evaluated in terms of the delay in tumor growth. Tumor growth was delayed greatly with increase in the duration of treatment with 44 degrees hyperthermia, whereas with 42 degrees hyperthermia of up to 180 min, tumor growth was delayed only slightly. The effects of step-up heating were similar to those of 44 degrees hyperthermia alone and the response was enhanced by a factor of 0.9-1.1 with the 60-min treatment at 42 degrees followed by treatment at 44 degrees. Thermal resistance developed when the preheating time at 42 degrees was longer than 30 min. On the other hand, the tumor response was markedly enhanced by step-down heating by a factor of 1.8-2.4 with the treatment at 44 degrees followed by 60-min treatment at 42 degrees. Since the enhancement factor for skin damage found previously was similar to that for the tumor, therapeutic gain cannot be expected by the use of these combined heat treatments.