Immunocytochemical and electrophysiological studies indicate the existence of a functional relationship between Cholecystokinin (CCK) and dopaminergic transmission. In order to gain more information on this relationship, the effect of Caerulein, a CCK stable analogue, on rat spontaneous locomotor activity and on biochemical markers of dopaminergic transmission were measured simultaneously. The concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) and the spontaneous or K+ evoked release of dopamine were studied in rat striatum and nucleus accumbens immediately after testing for motor activity. An almost complete reduction in locomotor activity but not significant changes in DOPAC content and dopamine release were observed in rats injected with the peptide (0.25/microgram/Kg, intraperitoneally). DOPAC concentrations were slightly (30%) decreased by increasing 200 folds caerulein dose. In addition, a very minute dose of haloperidol (25 /microgram/Kg) potentiated the caerulein (0.25/microgram/Kg) induced hypomotility, while the parameters of dopaminergic metabolism were unaffected. Our results indicate the existence of a relevant pharmacological interaction between caerulein and dopamine antagonists, although it is not clear whether this interaction takes place at the dopamine terminals level.