Evidence has accrued that nitric oxide (NO) is an effector molecule in cell-mediated immunity, and it is generally agreed that fever is beneficial to host defence. Therefore, the role of elevated temperature in the induction of NO synthesis was examined in rat peritoneal macrophages activated by lipopolysaccharide (LPS). When macrophages were incubated in vitro at 40 degrees C, the time between macrophage activation and the induction of NO synthesis, as assessed by nitrite accumulation in the medium, was shortened as compared with incubation at 37 degrees C, and nitrite accumulation was markedly enhanced by 2.6- and 1.8-fold after 6 and 9 h of LPS activation, respectively. These results suggest that elevated temperature may contribute to enhance host defence by accelerating and amplifying the induction of NO synthesis in macrophages.