To assess whether peripheral immune stimuli activate sensory afferents at behaviorally active doses, we measured the effects of lipopolysaccharide (LPS) on the levels of sensory neuropeptides in the spinal cord. LPS (10 micrograms/mouse i.p.) increased the levels of substance P, neurokinin A, and calcitonin gene-related peptide in the spinal cord, the maximum being observed 1 hr post-injection. Pretreatment with indomethacin at a dose (5 mg/kg i.p.) which completely blocked the decrease in food-motivated behavior induced by LPS abrogated this effect.