The purpose of this study, in part, was to determine the ability of cholecystokinin (CCK-33/39 and CCK-8) to penetrate the blood cerebrospinal fluid (CSF) barrier in dogs by measuring these forms of CCK in plasma and in CSF. In addition, the effectiveness of centrally administered bombesin in releasing brain CCK-33/39 and CCK-8 was evaluated. Six groups of five dogs each were studied. Each group received one of the following: (1) intravenous infusion of CCK-33/39 (1.3 micrograms/kg/hr); (2) intravenous infusion of CCK-8 (0.4 micrograms/kg/hr); (3) intrathecal infusion of CCK-33/39 (1.3 micrograms/kg/hr); (4) intrathecal infusion of CCK-8 (0.5 micrograms/kg/hr); (5) intravenous infusion of bombesin (1 micrograms/kg/hr); and (6) intrathecal infusion of bombesin (1 microgram/kg/hr). Plasma concentrations of CCK-33/39 significantly increased during intravenous infusion of CCK-33/39 (from basal of 84 +/- 8 to 142 +/- 2 pg/ml) or bombesin (from basal of 78 +/- 13 to 325 +/- 87 pg/ml); however, CSF perfusate concentrations of CCK-33/39 did not increase. CCK-33/39 levels of the CSF perfusate increased significantly (P less than .05) from 211 +/- 84 to 9,873 +/- 3,368 pg/ml during intrathecal infusion of CCK-33/39, but failed to rise simultaneously in the systemic circulation. Similarly, intravenous infusion of CCK-8 caused a fivefold elevation in plasma CCK-8 levels and no change in CSF perfusate levels of CCK-8; moreover, intrathecal infusion of CCK-8 failed to elevate peripheral CCK-8 levels, despite CSF perfusate CCK-8 levels of 92,300 +/- 18,598 pg/ml. Intrathecal concentrations of neither CCK-33 nor CCK-8 were affected by intravenous or intrathecal administration of bombesin. We conclude that CCK-33/39 and CCK-8 do not penetrate the blood-cerebrospinal fluid barrier in dogs, and centrally administered bombesin is ineffective in causing release of cholecystokinin from brain tissue into the CSF.