The effect of sulfated cholecystokinin (CCK-8S) on acetylcholine turnover (TRACh) and dopamine (DA) release in the rat cerebral cortex and striatum was studied in unanaesthetized animals in vivo. CCK-8S (1 mg/kg s.c.) decreased TRACh in the fronto-parietal cortex but not in the striatum. This effect was prevented by peripheral (10 mg/kg i.p.) but not central (1 microgram i.v.t.) administration of the peripheral CCK receptor antagonist CR 1409. In a separate study, CCK-8S decreased 3-methoxytyramine (3-MT) levels (an index of DA release) in the fronto-parietal cortex and in the striatum. CR 1409 appeared to have a partial agonist action, reducing cortical and striatal 3-MT levels, and only partially reversing the effect of CCK-8S in the striatum. These data indicate that peripheral administration of CCK-8S decrease TRACh in the cortex but not in the striatum and that this action is mediated by peripheral-type CCK receptors possibly located outside the CNS. CCK-8S also reduces DA release in the cortex and in the striatum, and this effect appears to be mediated by a mechanism of action different from that modulating cortical TRACh.