Bacterial lipopolysaccharide (LPS) suppresses feeding in rats when administered peripherally in the microgram range. In the present study, the effects of LPS (Escherichia coli serotype 0111:B4) on the central regulation of feeding in rats maintained ad lib was investigated. Intracerebroventricular (ICV) microinfusion of LPS (0.1 to 1000 ng/rat) suppressed the short-term (2-h) and long-term (nighttime and total daily) food intakes, dose dependently. Computerized analysis of behavioral patterns demonstrated a significant reduction of meal size during the nighttime, whereas meal frequency and meal duration were also decreased, but not significantly. Water intake and locomotor activity also decreased. Intraperitoneal administration of LPS in doses equivalent to those administered centrally had no effect on food intake. The results suggest that centrally administered LPS acts directly in the central nervous system (CNS) to depress feeding.