Two predominant WBH protocols presently being used in clinical trials include a low temperature, long duration (LL) WBH, where core body temperature is raised to 39.5-40 degrees C for 6h or more, and a high temperature, short duration (HS) WBH, where core body temperature is raised to 41.8 degrees C for up to 2h. Here, the effects of LL-WBH and HS-WBH on leukocyte populations in the blood, spleen, lymph node (LN) and peritoneal cavity (PerC) of Balb/c mice were compared using flow cytometry. The total numbers of peripheral blood leukocytes decreased up to 2-fold immediately after LL-WBH, reflecting a decrease of lymphocyte numbers compared to controls. In contrast, the numbers of blood leukocytes are increased 2.7-fold immediately after HS-WBH compared to controls, reflecting an increase in lymphocytes, monocytes and granulocytes. After both LL- and HS-WBH treatment, leukocyte numbers in the spleen are decreased approximately 2-fold, again reflecting decreases in lymphocyte numbers. In the PerC, total numbers of leukocytes are also significantly decreased (2-fold) during LL-WBH but not HS-WBH. Total numbers of leukocytes in the LNs were unaffected by both LL- and HS-WBH. Overall, these data reveal differential effects of the LL- and HS-WBH protocols on leukocyte populations in the blood, spleen, LN and PerC of Balb/c mice.