To determine whether conventional hyperthermia (42-45 degrees C) or ablation therapy (>50 degrees C) achieves better synergistic effects on direct cytotoxicity and anti-tumor immunity, we compared the therapeutic effects of two hyperthermia temperatures, 43 and 55 degrees C, in terms of cytotoxicity and upregulation of immune functions in a mouse malignant melanoma model. Melanoma-bearing mice were treated by directly applying regional hyperthermia to the tumor nodule with a heating light at a temperature of 43 degrees C for 30 min or 55 degrees C for 10 min. The tumor growth curve and mice survival rate were observed. To investigate the hyperthermia-induced immunological response, peripheral blood CD4(+) and CD8(+) T cells and the serum IL-2 level were determined. Our results indicated that application of regional hyperthermia at the ablation temperature (such as 55 degrees C) achieved better synergistic anti-tumor effects than did conventional hyperthermia (43 degrees C). Significant increases in the number of peripheral blood CD4(+) T cells and the serum IL-2 level likely contributed to the underlying mechanism. (C) 2009 National Natural Science Foundation of China and Chinese Academy of Sciences. Published by Elsevier Limited and Science in China Press. All rights reserved.