The relationship between cerebrospinal fluid and plasma cholecystokinin (CCK) levels was investigated by simultaneous withdrawal of CSF and blood from anesthetized mongrel dogs and measurement of CCK immunoreactivity by radioimmunoassay. A significant correlation occurred between CSF and plasma levels of CCK. During a CCK IV infusion, a statistically significant inverse correlation was noted between CSF and plasma values, while no significant relationship was noted during a bombesin (BBS) IV infusion. When infusion data were analyzed together with the appropriate baseline data, polynomial analysis revealed significant biphasic relationships for both CCK and BBS infusion studies. Intraventricular infusion of CCK did not alter plasma levels. These data suggest that existence of a mechanism relating CSF to plasma CCK levels (a gut to brain axis) with possible modulation or suppression by BBS.