To the Editor: For nearly three decades, researchers have hypothesized that neurotensin is an endogenous neuroleptic (1). This idea is based on animal behavioral studies that showed marked similarities between antipsychotic drugs and neurotensin, which needs to be directly injected into the brain to cause its CNS effects. In fact, in some behavioral paradigms, neurotensin acts like an atypical antipsychotic drug (2). More recently, researchers showed that antipsychotic drugs rapidly increase the expression and release of neurotensin. Therefore, it has been suggested that the therapeutic effects of antipsychotic drugs are mediated by endogenous neurotensin (3). Indeed, in rodent models that are predictive of antipsychotic activity, a neurotensin receptor agonist (NT69L) that we have under development and that is able to cross the blood-brain barrier acts like an atypical antipsychotic drug (4, 5). Therefore, we were not surprised to learn from the article by Herbert Y. Meltzer, M.D., et al. (6) that a neurotensin receptor antagonist, SR48692, had no efficacy in treating schizophrenia.