Interactions of neurotensin (NT) with midbrain dopamine (DA) neurons were studied in rats using microiontophoretic techniques. Local ejection of NT significantly increased (greater than 30%) the firing rate of a few DA cells (12/106). In most cases, however, iontophoretic NT produced no significant change in spontaneous activity. On the other hand, in these same cells, NT significantly attenuated the inhibition induced by either DA or quinpirole, a specific D2 agonist. Inhibition induced by DA was not attenuated by either glutamate or cholecystokinin, although both of them increase the firing rate of DA cells. The effect of NT appears to be selective as NT attenuated DA-induced inhibition without a measurable effect on either GABA-induced inhibition or glutamate-induced excitation of the same DA cells. Combined, these results suggest that NT's effect on DA cell activity is primarily a neuromodulatory one. As both NT and D2 receptors in midbrain DA cell areas are primarily located on DA cells, the above results also suggest that the observed interaction between NT and DA occurred at the DA cell level.