Background: An activation of the immune system might contribute to the therapeutic effect of WBH in cancer patients. We explored immune and endocrine responses in patients undergoing high-temperature WBH. Identical parameters were investigated in a separate group of healthy volunteers undergoing physical exercise to rule out effects of sympathetic activation. Methods: Lymphocyte subpopulations, lymphocytic expression of a range of adhesion molecules and serum concentrations of a variety of hormones and cytokines were assessed in cancer patients undergoing high-temperature (60 minutes at 41.0 to 41.8 °C) WBH (n=25) and in a separate group of healthy volunteers (n=10) performing strenuous physical exercise. Results: WBH induced an increase in human growth hormone, ACTH, and cortisol as well as in TNF-, IL-6, IL-8, and IL-12R. We observed an increase in NK cells and CD56⁺ NK T cells shortly after initiation of WBH. In contrast, we found a decrease in T cells expressing L-selectin (CD62L) or 47 integrin, adhesion molecules mediating homing to lymphatic tissues. Accordingly, we observed a decrease in CD45RA+CCR7+ "naive" and CD45RA-CCR7+ "central memory" T cells. Numbers of CD45RA-CCR7- "memory effector" and CD45RA+CCR7 "terminally differentiated" T cells, on the other hand, remained unchanged. No comparable changes were observed in the group of healthy volunteers. Conclusions: Patients with solid tumors treated with WBH show an increase in NK and NK T cells. In a later phase, plasma concentrations of IL-8, hGH, and cortisol increase, correlating with an influx of neutrophils into the peripheral blood. The alterations in T cell populations suggest that WBH may induce naive and central memory T cells to enter lymphatic tissue in order to await antigen exposure and effector T cells to migrate into peripheral tissues to exert their effector function. Although the exercise group may not be an appropriate control to proof the effect of WBH, these changes were not seen in the healthy volunteers performing physical exercise.