Intracellular recordings were obtained from rat ventral pallidal (VP) and mediodorsal thalamic (MD) cells in vivo and the effects of antipsychotic drugs on their basal and evoked electrophysiological characteristics were assessed. Administration of either haloperidol or clozapine caused a significant decrease in the average firing rate, accompanied by a hyperpolarization of the membrane potential in the VP cells recorded. However, neither drug induced a substantial change in the other basic membrane properties of the MD cells or VP cells tested. In addition, in 50% of the MD cells tested, both antipsychotic drugs caused a change in spike discharge from an oscillatory pattern to a tonic discharge mode. In rats that had received ibotenic acid lesions of the prefrontal cortex (PFCtx) 4-8 weeks prior to recording, cells in the VP exhibited similar changes in firing frequency in response to haloperidol administration as those in the intact rats. However, in contrast to the intact rats, MD cells recorded from rats with PFCtx lesions exhibited a significant increase in firing rate after haloperidol administration. The results from this study suggest that the prefrontal cortex plays a role in modulating the response of the thalamus to antipsychotic drugs.