To evaluate the role of subdiaphragmatic vagal afferent fibers in mediating the inhibition of food intake produced by peripheral administration of bacterial lipopolysaccharide (LPS) and the proinflammatory cytokine interleukin-1 beta (IL-1 beta), we assessed the ability of 100 micrograms/kg ip LPS and 2 micrograms/kg ip human recombinant IL-1 beta to suppress solid food intake during the first 3 and 6 h of the dark cycle in rats with selective vagal rootlet deafferentation (SDA, n = 15) and in sham surgical control rats (Con, n = 17). SDA was produced by a combination of dorsal subdiaphragmatic truncal vagotomy and left vagal afferent rootlet transection as the left vagus enters the caudal brain stem. Both LPS and IL-1 beta significantly suppressed food intake at 3 and 6 h in both Con and SDA rats, and SDA failed to attenuate the LPS- and IL-1 beta-induced reductions in food consumption relative to the suppression seen in controls. Peripheral administration of the gut-brain peptide cholecystokinin (CCK) suppressed 30-min 12.5% liquid glucose consumption in control, but not in SDA rats, consistent with previous demonstrations of the role of subdiaphragmatic vagal afferents in the mediation of CCK satiety. These data demonstrate that subdiaphragmatic vagal afferents are not necessary for the feeding-suppressive actions of peripherally administered LPS and IL-1 beta and suggest that peripheral LPS and IL-1 beta may inhibit food intake via humoral and/or splanchnic visceral afferent pathways.