The effect of moderate whole body hyperthermia (WBH) on the immunological responses of cancer patients was studied by monitoring their peripheral blood mononuclear cells (PBMC) in vitro. WBH of 2 degrees C above normal body temperature was induced in patients by utilizing a 433 MHz microwave system with a series of 6-9 external antennae. A total of three treatments were given with a frequency of one per week. Blood samples were drawn before treatment, when the target temperature was attained, and one hour after heating was discontinued. Changes in the number of PBMC, the mitogenic response, natural killer cell activity, and the production of Interleukin-1, Interleukin-2, and Interferon (IL-1, IL-2, IF) were measured in vitro. Mitogenic responses were increased 2-3 fold when the temperature was raised. Although there was an increase in the number of PBMC, during the course of heating, repeated treatment resulted in a selective and transient reduction in the number of PBMC. Nevertheless, the PBMC were capable of producing a higher level of cytokines and attained an enhanced ability to destroy target cells in vitro. The results indicate that, by inducing a fever-like condition, the immunological responses are enhanced in vitro.