Intraintestinal infusion of oleic acid reduces food intake in rats and other mammals. The neural mechanisms that mediate this behavioral response to intestinal stimulation are incompletely appreciated. We have found that intraintestinal infusion of capsaicin reduces sham feeding. In addition, 24 h after a single intestinal capsaicin infusion, reduction of sham feeding by intestinal oleate infusion was attenuated. However, by 48 h post-capsaicin, suppression of sham feeding by oleate had returned to pre-capsaicin levels. Repeated intestinal administration of capsaicin produced less attenuation of oleate-induced suppression of sham feeding, suggesting the development of tolerance to capsaicin. Unlike systemic capsaicin, intestinal capsaicin does not impair cholecystokinin-induced reduction of feeding or the corneal chemosensory reflex. Furthermore, there are no histochemical signs of vagal sensory degeneration in the hindbrain after intraintestinal capsaicin. Our results suggest that a capsaicin-sensitive substrate in or near the intestine is responsible for mediating the reduction of sham feeding by intestinal oleate infusion.