Cholecystokinin is a gastrointestinal peptide which is released from the duodenum during eating. Cholecystokinin octapeptide (CCK-8) has been found to improve retention when administered intraperitoneally in intact mice but not in vagotomized mice. This suggested that CCK-8 improves retention by stimulating vagal afferents to the nucleus of the solitary tract in the brainstem. In this study, we tested whether nerve fibers in the stria terminalis which project from the NTS to the amygdala need to be intact for CCK-8 to enhance retention. Three groups of mice were used: nonoperated, bilateral cortical control lesioned, and bilateral stria terminalis lesioned. The lesions were performed 1 week prior to footshock avoidance training in a T-maze. Saline, CCK-8 (0.5 microgram/kg, ip), epinephrine (100 micrograms/kg, sc), or arecoline (1.5 mg/kg, sc) were administered immediately after training. Retention was tested 1 week later. Neither bilateral stria terminalis lesions nor cortical control lesions significantly altered acquisition of the task compared to the nonoperated group. Whether the groups received a saline injection after training or received no injection did not affect retention test performance. CCK-8 and epinephrine enhanced retention in the mice with cortical lesions but not in mice with stria terminalis lesions. Arecoline enhanced retention in both groups. Possible pathways and neurotransmitters mediating the effect are discussed.