Experiments were conducted to determine the effect of injection of lipopolysaccharide (LPS, from S. typhimurium) or muramyl dipeptide (MDP, N-acetylmuramyl-L-ala-isoglutamine) in Japanese quail. Doses of MDP between 0.3 and 10 mg/kg body wt. had no effect on body temperature. In contrast, doses of 1.0-22.5 mg LPS/kg body wt. caused significant increases in body temperature. None of the doses of LPS or MDP resulted in mortality. The febrile response to LPS was diminished following a second injection 48 h after the first, and was absent following a third injection. Plasma zinc, an indicator of the acute phase response, was significantly reduced by either LPS or MDP after the first injection (P<0.001), but not after the second or third injection. Splenic interleukin 1-beta (IL-1beta) mRNA expression was increased after the first and last injection of LPS (P<0.001), but only after the first injection of MDP (P<0.005). Hepatic IL-1beta mRNA expression was increased after the first, but not the third injection of LPS (P<0.001), while MDP had no effect. These data indicate that Japanese quail are less sensitive to MDP than LPS, and that quail demonstrate tolerance to LPS following repeated injections.