Rats received an injection of [14C]leucine and were then divided into four groups. Groups I and II consisted of ad libitum fed rats were administered saline or endotoxin of Salmonella enteritidis eight and twenty-two h after the [14C]leucine treatment. Animals of Group III (saline) and Group IV (endotoxin) fasted after [14C]leucine injection. Twenty three hours after [14C]leucine treatment rats were injected with pHjleucine and sacrificed 20 min afterwards. Endotoxin administration decreased body weight in fed rats only. After endotoxin treatment, higher [3H]leucine specific activity in the blood plasma, decreased leucine incorporation into proteins and lowered plasma amino acid levels were observed. [14C]leucine radioactivity was significantly higher in the spleen and lower in skeletal muscles of endotoxin-treated rats. All changes were less expressed in fasted than in ad libitum fed animals. Our results indicate that endotoxin treatment results in (a) changes in host metabolism that are not mediated solely by anorexia; (b) a decrease of protein synthesis in the viscera and skeletal muscles; (c) an increase of protein degradation in skeletal muscles; (d) reutilization of leucine released from skeletal muscles in viscera, and (e) a slower disappearance rate of leucine from the blood.