To examine the role of the liver in lipopolysaccharide (LPS)-induced hypophagia, we investigated the effect of hepatic portal and vena cava infusions (1 mL/30 min) of LPS (100 microg/kg of body weight) on feeding in rats. LPS infusion significantly reduced food intake when administered via either the hepatic portal vein or the vena cava. Both the magnitude and time course of this hypophagia were similar regardless of the infusion route. As in previous experiments of ours in which LPS was administered by intraperitoneal (i.p.) injection, LPS reduced food intake by decreasing meal frequency, without affecting meal size or duration. The results suggest that peripherally administered LPS does not act primarily in the liver to reduce food intake.