Local and systemic temperature change is associated with the immune response to infection, but the role of temperature remains poorly understood. To study the effect of temperature on macrophage activation by lipopolysaccharide (LPS), RAW 264.7 cells were incubated with LPS at different temperatures and secretion of three cytokines was measured. Incubation at 31 degrees C increased tumour necrosis factor (TNF) secretion when compared with 37 degrees C, while cells exposed at 39 degrees C secreted less TNF. Interleukin-6 (IL-6) secretion was less at 31 degrees C than at 37 degrees C and remained unchanged at 39 degrees C. Interleukin-10 secretion was depressed on either side of 37 degrees C. Only IL-6 secretion was sensitive to preincubation temperature effects. The kinetics of cytokine secretion and steady-state mRNA analysis indicated potentially different mechanisms of temperature regulation for TNF and IL-6.