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OBJECTIVE: The authors compared serotonin receptor binding in patients with schizophrenia and healthy comparison subjects.METHOD: They used positron emission tomography with [18F]setoperone to examine six patients with schizophrenia who had never been given neuroleptics and seven age-matched subjects who did not have schizophrenia.RESULTS: A nondirected voxel-based analysis of the subjects’ entire search volume found that serotonin 2A binding potential in the frontal cortex index was significantly smaller (by 16.3%) in patients with schizophrenia than in healthy subjects.CONCLUSIONS: The authors conclude that the decrease in serotonin receptor densities previously reported in postmortem studies of subjects with schizophrenia are present at the onset of the illness, before exposure to neuroleptics.