Peptides from cocaine- and amphetamine-regulated transcript (CART) reduce food intake in rats when injected into the lateral ventricle. Hypothalamic and hindbrain sites important in the control of feeding contain CART-immunoreactive fibers. To further define the site of CART's anorectic action, we compared feeding and other behavioral responses to third or fourth ventricular (3V, 4V) CART-(55-102) in 6-h food-deprived rats, both before and after cerebral aqueduct occlusion. 3V CART reduced the volume of Ensure consumed and resulted in fewer observations of eating and grooming within the 30-min test session. These reductions were significantly attenuated by aqueduct obstruction. 4V CART suppressed Ensure intake and resulted in decreased observations of feeding both with and without aqueduct blockade. 3V CART produced flat-backed postures and movement-associated tremors that were prevented by aqueduct obstruction. 4V CART also produced these signs, both with and without aqueduct blockade. We conclude that the major hypophagic effect of intracerebroventricular CART is mediated at a hindbrain site. The association of CART-induced feeding suppression with altered motor behavior questions the specificity of intracerebroventricular CART for actions on feeding.