The present study mapped the topographic distribution of, and the effect of neuropharmacologically distinct antipsychotic drugs on, the concentration of neurotensin (NT) in the rat brain at the level of discrete nuclei or areas. The chronic administration of either haloperidol or clozapine increased the concentration of NT-like immunoreactivity (NT-LI) in the nucleus accumbens and decreased it in the medial prefrontal and cingulate cortex and in the interstitial (bed) nucleus of the stria terminalis. In contrast, the prolonged administration of haloperidol, but not clozapine, increased the concentration of NT-LI in the anterior caudate nucleus and posterior caudate-putamen. The concentration of NT-LI in the great majority of the rat brain nuclei examined was unaffected by the chronic administration of either antipsychotic drug. This pattern of pharmacological response distinguishes NT from all other neuropeptides which have been shown to be influenced by prolonged antipsychotic drug administration. These findings suggest that the functional information imparted to NT-containing cells by neuronal dopamine (DA) release, as inferred from the consequences of receptor blockade, varies remarkably between different populations of DA neurons and further implicate NT as a neuroanatomically-selective neurochemical substrate of the adaptive responses mediating the therapeutic and motoric side effects of antipsychotic drugs.