Cholecystokinin octapeptide (CCK-8) exists in a subpopulation of midbrain dopaminergic (DA) neurons and has been shown to affect the activity of unidentified DA cells. This study describes the effects of the sulfated (CCK-8S) and unsulfated (CCK-8US) peptides (8 micrograms/kg, i.v.) on the ability of apomorphine to inhibit the firing rate of nigrostriatal DA cells identified by antidromic activation from the caudate nucleus of anesthetized rats. CCK-8S excited 9/25 DA cells while CCK-8US was without effect on firing rate (n = 9). CCK-8S pretreatment resulted in complex changes in the sensitivity of nigrostriatal DA cells to apomorphine which were related to whether an initial excitatory response was elicited by CCK-8S. CCK-8US did not alter apomorphine sensitivity. These results suggest that CCK-8S can exert modulatory effects on DA cells independent of a direct excitatory action. The effect of acute CCK-8 injection on the number of spontaneously active DA cells in stereotaxically defined regions of the substantia nigra and ventral tegmental area was also determined. CCK-8S doubled the number of active cells in these areas; CCK-8US did not alter the population activities.