Effects of prefrontal cortex microinjections of 0.3 and 3 nmol/0.5 microl of neurotensin-(8-13) on the firing rate of midbrain dopamine and non-dopamine cells were studied in urethane-anesthetized rats. Neurotensin produced an increase in firing in 14 of 26 dopamine cells tested, an effect that peaked between 15 and 20 min after the injection at both doses. On the other hand, a majority of non-dopamine cells (7/10) tested with the higher dose of neurotensin showed a statistically significant decrease in firing when compared to saline, an effect that also peaked between 15 and 20 min. These results show that prefrontal cortex neurotensin can modulate both dopamine and non-dopamine neurotransmission in the ventral midbrain.