Changes in cholinergic neurons have been implicated in the pathology of schizophrenia. Clozapine, an atypical anti-psychotic drug, has been shown to bind with high affinity to the muscarinic1 (M1) receptor suggesting this receptor could be involved in the therapeutic efficacy of the drug. Because of this we measured the density of M1 receptors in the caudate-putamen, obtained at autopsy, from 19 schizophrenic subjects and 19 non-schizophrenic subjects. The density of M1 receptors was decreased in the caudate-putamen from the schizophrenic subjects (181 �� 20 vs 287 �� 10 fmol mg 1 TE; mean �� s.e.m.; P < 0.001). Furthermore, preliminary studies would not suggest that the change in the density of M1 receptors in the tissue from the schizophrenic subjects had resulted from drug treatment prior to death. These data raise the possibility that changes in muscarinic receptors may be involved in the pathology of schizophrenia.