Chronic treatment with neuroleptics has been reported to induce a status of depolarization inactivation of the majority of midbrain dopamine neurons. The present study was aimed at determining whether general anesthesia might be a contributory cause of depolarization inactivation of substantia nigra dopamine neurons. In agreement with previous studies, where neuronal sampling was carried out in animals under chloral hydrate anesthesia, chronic treatment with haloperidol (0.5 mg/kg daily for 21-28 days) produced a marked reduction (about 80%) in the number of spontaneously active dopamine neurons. However, when neuronal sampling was performed in unanesthetized rats, chronic administration of haloperidol (daily for 21-28 days) failed to reduce the incidence of active dopaminergic neurons. The results suggest that depolarization inactivation of dopamine neurons is not present in the intact animal but is probably produced during the neuronal sampling procedure as a consequence of neuroleptic-induced hyperexcitability of dopamine neurons combined with their stimulation by general anesthetics.