In response to inflammatory stimuli, macrophages synthesize and secrete prostaglandins (PGE) along with other potent inflammatory mediators. We have studied the effect of hyperthermia on the production of PGE by murine mononuclear phagocytes. Exposure to high temperature induced PGE production by cultured C3H/HeJ exudate macrophages in a time- and temperature-dependent manner. Increase in PGE production was detected when macrophages were treated at 41 degrees C and above for 1 h with a much greater increase at 42 and 43 degrees C. The secretion of PGE into culture supernatants by heat-treated macrophages reached a maximum approximately 24 h after heat treatment. The production of PGE by macrophages after hyperthermia was inhibited either by the addition of 5 X 10(-7) M indomethacin or by the subsequent incubation at 4 degrees C, suggesting that the elevated PGE production by macrophages is mediated through the activation of cyclooxygenase. Heat treatment under the same conditions failed to stimulate the production of PGE by either a human monocyte-like tumor cell line (U-937) or a mouse fibroblast cell line (L-929).