To determine whether lesions in the prefrontal cortex (PFC) alter the activity of midbrain dopamine (DA) neurons, single unit recordings were made from DA neurons in control and lesioned rats. PFC lesions, obtained by local injection of ibotenic acid into the medial PFC, had no effect on either firing rate or bursting activity of DA neurons in the ventral tegmental area (VTA). However, the number of spontaneously active DA neurons in the VTA was significantly decreased. In the substantia nigra (SN), the same lesions increased the firing rate and had no effect on either the bursting activity of the number of active DA cells. These results suggest that PFC lesions alter the activity of DA neurons. However, VTA and SN DA neurons may respond differently to PFC lesions.