Endogenous pyrogen (EP) and interleukin (IL 1) appear to be closely related or identical. We therefore conducted experiments to test whether the central action of EP (fever) enhanced its local action (potentiation of immune responses). We found that 3H-TdR incorporation by thymocytes stimulated with IL 1 in the presence of 5 micrograms/ml of phytohemagglutinin (PHA) was strongly enhanced by small rises of temperature in the 32 to 38 degrees C range. Responses at 40 degrees C were generally less than those seen at 38 degrees C. Calculated values for the temperature coefficient (Q10) of the PHA-facilitated response to IL 1 varied between 50 and 300 in different experiments. Thymocytes had a variable response to IL 1 in the absence of PHA. However, thymocytes that failed to agglutinate with peanut agglutinin responded consistently to IL 1 alone, and these mitogenic responses were strongly temperature sensitive (Q10, 50 to 100 in different experiments). Thymocyte responses to 5 micrograms/ml PHA were only modestly sensitive to temperature (Q10, 3 to 8), and responses to interleukin 2 gave Q10 values of 3 to 24, with a mean of about 9. The responses of CTL cells to IL 2 were also modestly enhanced by small increases of temperature, and calculated Q10 values were similar to those observed for thymocytes. IL 1 production by macrophages was also not greatly enhanced by temperature (Q10, 2 to 5). These observations suggest that small increases of temperature enhance IL 1 activity to a much greater degree than they enhance the activity of other components of the immune response. This may help to explain the conservation of two such apparently disparate activities as EP and IL 1 in the same molecules.