To assess the role of subdiaphragmatic vagal afferent and efferent fibers in the mediation of the inhibition of food intake by cholecystokinin (CCK), we compared the ability of a dose range (1-16 microg/kg), of CCK to affect 30-min liquid glucose (0.125 g/ml) intake in rats with either total subdiaphragmatic vagotomy, selective subdiaphragmatic vagal deafferentation, selective subdiaphragmatic vagal deefferentation, or sham surgery. Selective vagal deafferentation and deefferentations were produced by combinations of unilateral subdiaphragmatic vagotomy and contralateral afferent or efferent rootlet transection as fibers enter the caudal medulla. CCK produced a dose-related suppression of glucose intake in sham animals, and this action was eliminated in rats with total subdiaphragmatic vagotomy. CCK suppression of intake was attenuated in rats with vagal deafferentation, such that there was a loss of sensitivity to CCK. Vagal deefferentation resulted in lower levels of baseline intake and a truncation of the feeding-inhibitory actions of CCK. These data demonstrate that CCK's suppression of intake depends on actions of both vagal afferent and efferent fibers. We interpret these data as suggesting that 1) the actions of low doses of CCK depend on activation of vagal afferent CCK receptors and 2) the greater efficacy of higher CCK doses is the result of the potentiation of these vagal afferent actions due to local physiological gastrointestinal effects of the peptide that rely on vagal efferent input.