Functional evidence exists for a nose-brain pathway for the neuropeptide cholecystokinin-8 (CCK-8S). The transport mechanism, however, remains still unclear. Previous studies indicate a saturable dose-response curve on the magnitude of the late positive complex of the auditory event-related potential (AERP) with increasing doses of intranasally administered CCK-8S. Thus, the present study served to bypass this saturation by repeated lower dose intranasal administrations of CCK-8S. It was expected that this repetitive administration results in a nonsaturable dose-response effect on AERPs. AERPs reflecting cortical stimulus processing were recorded while subjects performed on an auditory attention task (oddball paradigm) four times (in intervals of 30 min) each following a separate 10-microg intranasal administration of CCK-8S or placebo. Compared with placebo, the repetitive intranasal administration of CCK-8S linearly enhanced the late positive complex and its subcomponent slow wave. Blood plasma CCK-8S levels were not affected by intranasal CCK-8S. The results suggest that by using a repetitive intranasal administration of CCK-8S, a saturable mechanism for central nervous CCK-8S effects can be avoided.