Kizaki, Takako, Tomomi Ookawara, Tetsuya Izawa, Junichi Nagasawa, Shukoh Haga, Zsolt Radák, and Hideki Ohno. Relationship between cold tolerance and generation of suppressor macrophages during acute cold stress. J. Appl. Physiol. 83(4): 1116-1122, 1997.Acute cold stress induces suppressor macrophages expressing large numbers of receptors to the crystallizable fragment (Fc) portion of immunoglobulin G (MAC-1⁺FcRII/III^bright cells), resulting in the immunosuppression of splenocyte mitogenesis. The generation of MAC-1⁺FcRII/III^bright cells is mediated by the action of glucocorticoids (GCs) through the GC-receptor. In the present study, the generation of MAC-1⁺FcRII/III^bright cells in peritoneal exudate cells was closely related to the decrease of rectal temperature during 3-day exposure to 5°C. We next investigated the effects of improved cold tolerance on the generation of MAC-1⁺FcRII/III^bright cells during acute cold stress. Mice were adapted to cold by exposure to 5°C for 3 wk (cold-acclimated mice) and then reexposed to 5°C for 3 h (acute cold stress) after living at 25°C for 24 h. The rectal temperature of cold-acclimated mice was not decreased by the acute cold stress. In addition, the proportion of MAC-1⁺FcRII/III^bright cells in peritoneal exudate cell population from cold-acclimated mice was unaffected by the acute cold stress. The cold acclimation significantly attenuated the increases in serum corticosterone levels and the expression of the GC-receptor mRNA on peritoneal exudate cells in response to acute cold stress. These results suggest that the altered GC response to acute cold stress by the improvement of cold tolerance inhibits the generation of suppressor macrophages during acute cold stress.