The present study was designed to determine whether whole body injection of lipopolysaccharide increases endogenous rat brain morphine levels. High performance liquid chromatography coupled to electrochemical detection and gas-chromatography mass spectrometry reveal that the resting brain morphine level is 7.0+/-3.2ng/g wet weight. In a time dependent manner, intraperitoneal injection of lipopolysaccharide (10 microg), leads to an increase of brain morphine level with a peak reaching after 36h post injection. After 72h following the lipopolysaccharide-injection, morphine levels increased to 66.0+/-5.4ng/g brain wet weight (P<0.001). Furthermore, 96h of fasting also increased the brain morphine level to 44.0+/-3. 6ng/g of brain wet weight. These results suggest that rat brain morphinergic processes respond to organismic challenges after a significant latent period.