Several lines of evidence, including the effect of antipsychotic drugs on neurotensin-containing neurons, have implicated the neurotensin system in the mechanism of action of antipsychotic drugs. Thus far, all clinically efficacious antipsychotics have been found to increase neurotensin concentrations in the nucleus accumbens; "typical" antipsychotic drugs increase neurotensin concentrations in both the nucleus accumbens and the caudate nucleus, whereas "atypical" antipsychotics increase neurotensin concentrations only in the nucleus accumbens. The effects of antipsychotic drugs on neurotensin-containing neurons in the nucleus accumbens may be predictive of clinical antipsychotic efficacy whereas the effects on neurotensin in the caudate nucleus may be predictive of extrapyramidal side effects. In addition to this evidence that antipsychotic drugs may act at least in part on neurotensin-containing neurons to produce their clinical effects is a considerable data base indicating that there are alterations in neurotensin-containing neurons in schizophrenia.